1、後基因體時代的生醫素養與倫理法制,陳錦生,John Naisbittin “Megatrends 2000”,你也許不懂生物科技但你不能不知道它的最新發展否則你就是縱容別人以上帝自居基因改造過的生物會不會破壞自然生態將來會不會有人頭馬之類的怪物出現人類憑什麼干預生命的奧秘過程科學家會不會唯利是圖 濫用科技你推卸不了道義責任,生物技術的世紀,1980年，第一個人工改造的細菌獲得專利1977年，桃麗羊複製成功2000年，人體基因組解碼獲初步成功基因工程技術的蓬勃發展複製人？,人體基因體計畫,人類基因體計劃（Human Genome Project）是由美國、英國、法國、德國、中國與日本等六國科學家
2、所組成的龐大團隊，經費大部份來自美國聯邦政府的國家衛生研究院（NIH）與英國的衛爾康基金會（WellcomeTrust）。賽雷拉公司（Celera Genomics）則是由科學界的傳奇人物文特博士所創立，在一九九八年以異軍突起之姿投入破解人類基因密碼的競技場，而且成果斐然。 但是繪製人類基因圖譜只是破解人類基因密碼的基礎，科學家必須進一步確認人體所有的基因、了解基因的功能與控制方式、基因與人體生理以及疾病的關聯，然後才能開發出嶄新的藥品與治療方式，其成果將為人類醫學與文明帶來革命性的進展與衝擊。,後基因體時代來臨,美國官方主導的國際人類基因體計劃與美國民間賽雷拉公司，在90年1月全球五大城市共
3、同發布他們解讀人類基因體的最新成果，而兩者含括人類基因體定序初稿與其解析的研究報告也分別刊載於自然與科學雜誌。 這兩份研究報告雖然運用的方法不同，但結論大致相近，其中有幾項發現最受矚目：人類基因的數目遠少於以往科學界的預估（十萬個），大約只有三萬到四萬個，僅僅是果蠅、線蟲等低等生物的兩倍多。而且與老鼠比較，人類只有三百餘個基因是老鼠身上找不到的。人類基因體計劃的領導人柯林斯說：這對我們人類的自尊是個打擊，不過這也顯示了人類的複雜性來自其他源頭，我們必須開始搜尋。,生物科技倫理議題,胚胎地位的爭議基因改造食品人體基因計畫複製技術帶來的社會衝擊生殖科技幹細胞基因行為學,動物權基因專利及商業化生物資
4、料庫(biobank)宗教議題生態衝擊,何謂醫學倫理學四大原則？,尊重自主原則(the principle of respect for autonomy)、不傷害原則(the principle of nonmaleficence)、行善原則 (the principle of beneficence) 公平正義原則(the principle of justice)。,後基因體時代的生技倫理,1960年生物倫理學成為專門領域1992年，美國各院醫院規定必須要有生物倫理學家駐院，或訂定醫學倫理準則。2000年人體基因體解碼完成，進入後基因體時代。後基因體時代的生技倫理學不是因應醫學的新發展，
5、而是預測新科技可能帶來的貢獻和災害。,BioethicsScience asks Can we?Law asks May we?Morality asks Should we?,韓複製專家黃禹錫因卵子風波辭卸所有職務,以複製世界上第一隻複製狗Snuppy而揚名於世的南韓幹細胞研究權威、首爾大學教授黃禹錫，因獲取科研用卵子的過程而引發的道德倫理風波，今天宣佈辭去包括首爾國際幹細胞研究中心主任等所有在政府和民間機構的兼職。 截止到25日，黃禹錫教授崇拜者俱樂部“我愛你，黃禹錫( 東山半夜會（音譯）、佛教人權委員會、大韓佛教青年會、佛教生命倫理研究所等12個佛教團體成立了“爲黃禹錫博士的韓國在家修行
6、者聚會。”,南韓複製爆醜聞 錢換卵子 黃禹錫承認違反醫事倫理 為隱瞞真相道歉辭職 韓人仍力挺,南韓複製爆醜聞，蜚聲國際的複製先驅黃禹錫(Hwang Woo-suk，圖，美聯社)24日召開記者會，承認明知其團隊兩名女研究員捐卵供研究之用，卻應當事人之請未向外吐實，承認違反醫事倫理，為隱瞞真相道歉辭職。,從孟德爾開始,Gregor Mendel (1822-1884)在孟德爾之前，大部分人相信遺傳混合學說(blending theory of iheritance)孟德爾的豌豆實驗,1953年英國劍橋大學博士生詹姆斯華生（James D. Watson），及法蘭西斯克立克（Francis Cric
7、k ）發現的雙螺旋結構，證實了是所有生命的核心,A structure for Deoxyribose Nucleic Acid The year 1953 could be said to mark, in biology at least, the end of history. Here is James Watson and Francis Cricks paper on the structure of DNA, which ushered in the new era with the celebrated understatement near the end. (as publ
8、ished in NATURE magazine)2 April 1953MOLECULAR STRUCTURE OF NUCLEIC ACIDSA Structure for Deoxyribose Nucleic AcidWe wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest. A structure for nucleic
9、acid has already been proposed by Pauling and Corey (1). They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfact
10、ory for two reasons: (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other. (
11、2) Some of the van der Waals distances appear to be too small.Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defin
12、ed, and for this reason we shall not comment on it.We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis (see diagram). We have made the usual chemical assumptions, namely, that each chai
13、n consists of phosphate diester groups joining -D-deoxyribofuranose residues with 3,5 linkages. The two chains (but not their bases) are related by a dyad perpendicular to the fibre axis. Both chains follow right- handed helices, but owing to the dyad the sequences of the atoms in the two chains run
14、 in opposite directions. Each chain loosely resembles Furbergs2 model No. 1; that is, the bases are on the inside of the helix and the phosphates on the outside. The configuration of the sugar and the atoms near it is close to Furbergs standard configuration, the sugar being roughly perpendicular to
15、 the attached base. There is a residue on each every 3.4 A. in the z-direction. We have assumed an angle of 36 between adjacent residues in the same chain, so that the structure repeats after 10 residues on each chain, that is, after 34 A. The distance of a phosphorus atom from the fibre axis is 10
16、A. As the phosphates are on the outside, cations have easy access to them.The structure is an open one, and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.The novel feature of the structure is the manner in
17、which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis. The are joined together in pairs, a single base from the other chain, so that the two lie side by side with identical z-co-ordinates. One of the pair must be a puri
18、ne and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows : purine position 1 to pyrimidine position 1 ; purine position 6 to pyrimidine position 6.If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the k
19、eto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are : adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine).In other words, if an adenine forms one member of a pair, on either chain, then on t
20、hese assumptions the other member must be thymine ; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then th
21、e sequence on the other chain is automatically determined.It has been found experimentally (3,4) that the ratio of the amounts of adenine to thymine, and the ration of guanine to cytosine, are always bery close to unity for deoxyribose nucleic acid.It is probably impossible to build this structure w
22、ith a ribose sugar in place of the deoxyribose, as the extra oxygen atom would make too close a van der Waals contact. The previously published X-ray data (5,6) on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the
23、 experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications. We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely
24、 on published experimental data and stereochemical arguments.It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.Full details of the structure, including the conditions assumed in building it, together
25、with a set of co-ordinates for the atoms, will be published elsewhere.We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances. We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas
26、of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at Kings College, London. One of us (J. D. W.) has been aided by a fellowship from the National Foundation for Infantile Paralysis.J. D. WATSON F. H. C. CRICK Medical Research Council Unit for the Study of Molecular Structure of Biolog
27、ical Systems, Cavendish Laboratory, Cambridge. April 2.1. Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S. Nat. Acad. Sci., 39, 84 (1953). 2. Furberg, S., Acta Chem. Scand., 6, 634 (1952). 3. Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff, E., Biochim. e
28、t Biophys. Acta, 9, 402 (1952). 4. Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952). 5. Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ. Press, 1947). 6. Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta, 10, 192 (1953).VOL 171, page737, 1953,基因科技,基因Gene,基因位於染色體上，是
29、一段DNA序列。基因可以指引特定的胺基酸序列形成，而形成特定的蛋白質。基因的特性：具備調控細胞或生物的發育與代謝、行為能力的訊息。細胞分裂時，能穩定且高度正確的複製，方能使這訊息物質代代相傳。能夠產生突變，以產生演化過程中的遺傳變異。,基因工程,剪刀：限制酶(restriction nuclease )醬糊：連結酶(Ligase)交通工具：載體(Vector)目的地：宿主 (Host),基因工程的應用,醫學：胰島素、B肝疫苗、生長激素、複製製藥活體工廠、IQ基因、疾病檢測（25 oncogens、糖尿病、巴金森、老化）、生殖技術農學：超級蕃茄、吃豆如吃肉、快速生長之家畜、環境：分解原油、鎘米、
30、可分解的塑膠袋法醫：鑑定、微量證據、微量證據、親子鑑定、PCR其他：化工,基因工程的影響,影響：既興奮又害怕（科學樂觀派vs.科學悲觀派）新優生學：基因族vs.自然族（何謂優？）對症療法vs.對因療法基因決定我們vs.我們決定基因基因歧視、基因隱私（如果嬰兒基因有缺陷）基因單一化（缺乏多樣性）商業化、專利化（有錢才能享受）科學解問題或製造問題？chance vs. choices; profit vs. problem; change vs. challenge,基因組是什麼？,基因組就是一個生命體的遺傳信息的總和。那麼在這裏我們就不是單個基因，而是所有的基因。它所編碼所有的氨基酸相互之間的這
31、個關係。,人體基因組研究,What is the Human Genome Project?,U.S. govt. project coordinated by the Department of Energy and the National Institutes of Healthgoals (1998-2003)identify the approximate 30,000 genes in human DNAdetermine the sequences of the 3 billion bases that make up human DNAstore this informatio
32、n in databasesdevelop tools for data analysisaddress the ethical, legal, and social issues that arise from genome research,Why is the Department of Energy involved?,after atomic bombs were dropped during War War II, Congress told DOE to conduct studies to understand the biological and health effects
33、 of radiation and chemical by-products of all energy production-best way to study these effects is at the DNA level,Whose genome is being sequenced?,the first reference genome is a composite genome from several different peoplegenerated from 10-20 primary samples taken from numerous anonymous donors
34、 across racial and ethnic groups,The human and chimp genomes are about 99.2% identical. Facts,size of human genome: 3.4 billion base pairs (bp)number of human genes: 100,000實驗室常用的大、小鼠的基因體據估有3萬個基因。另一實驗室常用生物的線蟲（C. elegans），其基因總數約有1萬9千個，而果蠅則有約1萬3千個。小型開花植物阿拉伯芥（Arabidopsis）的2萬7千個基因搞不好就比人類的還多。 genes vary
35、 in length and can cover thousands of bases - avg. size: 3,000 bponly about 5% of the human genome contains genesfunction of much of the genome is unknown,Chromosome: 1,Chromosome: 4,第一個完整中國人基因組圖譜繪製完成2007-10-11 19:05:53來源: 新華社(北京),中國科學家2007年10月11日對外宣佈，他們已經成功繪製完成第一個完整中國人基因組圖譜(又稱“炎黃一號”)，這也是第一個亞洲人全基因序列
36、圖譜。,黑猩猩基因定序 台灣有成2004/5/28,在解開人類第四對染色體鹼基定序、靈芝基因定序之後，國內基因研究再度締造了傲人記錄，台灣團隊兩年前加入了國際定序團隊，在基因體醫學國家型科技計畫的經費支持下，順利完成了世界首例精確定序的非人類靈長類物種染色體黑猩猩第22號染色體定序，正確率高達99.998%。 這項研究係由國家衛生研究院與陽明大學所組成的基因定序團隊執行，歷經兩年多終於完成了黑猩猩第22號染色體3330萬個鹼基的定序及比較分析黑猩猩是和人類最接近的哺乳類動物，兩者基因差異只有1.5%，大腦認知功能也最接近，而黑猩猩第22號染色體與人類第21號染色體相當，這項研究結果將有助於釐清
37、人類阿茲海默氏症、帕金森氏症等腦部退化疾病的致病機轉。下一步研究人員將透過基因解碼找出致病基因，並對人類生理及行為特徵形成的相關研究，提供先驅指標。 國衛院表示，這項成果對於人類的進化演變，更帶來了突破上的進展，先找出人猿演化成人類的分歧點，破解人類演化之謎。,Benefits of HGP ResearchMedical Benefits,improved diagnosis of diseaseearlier detection of predispositions to diseaserational drug designgene therapy and control systems
38、 for drugspharmacogenomics personal drugsorgan replacement,gene therapy,Benefits of HGP ResearchMicrobial Genome Research,new energy sources (biofuels)生物燃料(Biofuels)是指以生物質為載體的能源，直接或間接地源於植物的光合作用，例如乾草、渣滓、牛糞等等。不同於石油、煤炭、核能等傳統燃料，這新興的生物燃料是種可再生燃料。另一種定義是至少80的體積，由10年內生產的有機活體物質所提煉出的燃料。environmental monitoring
39、 to detect pollutantsprotection from biological and chemical warfaresafe, efficient toxic waste cleanup,Benefits of HGP ResearchDNA Forensics,identify potential suspects at crime scenesexonerate wrongly accused personsidentify crime and catastrophe victimsestablish paternity and other family relatio
40、nsidentify endangered and protected species as an aid to wildlife officials (prosecution of poachers),Benefits of HGP ResearchDNA Forensics cont.,detect bacteria and other organisms that may pollute air, water, soil, and foodmatch organ donors with recipients in transplant programsdetermine pedigree
41、 for seed or livestock breedsauthenticate consumables such as caviar and wine,Benefits of HGP ResearchAgriculture and Livestock,disease-, insect- and drought-resistant cropshealthier, more productive, disease-resistant farm animalsmore nutritious producebiopesticidesedible vaccines incorporated into
42、 food productsnew environmental cleanup uses for plants like tobacco,biopesticides蘇力菌(Bti),Benefits of HGP ResearchEvolution and Human Migration,use germline mutations in lineages to study evolutionstudy migration of different population groups based on female genetic inheritancestudy mutations on t
43、he evolutionarily stable Y chromosome to trace lineage and migrationcompare breakpoints in the evolution of mutations with ages of populations and historical events,Human Migration,Benefits of HGP ResearchRisk Assessment,assess health damage and risks caused by radiation exposure, including low-dose
44、 exposuresassess health damage and risks caused by exposure to mutagenic chemicals and cancer-causing toxinsreduce the likelihood of heritable mutations,Ethical, Legal, and Social Issues,The U.S. Department of Energy (DOE) and the National Institutes of Health (NIH) have devoted 3% to 5% of their an
45、nual Human Genome Project (HGP) budgets toward studying the ethical, legal, and social issues (ELSI) surrounding availability of genetic information. This represents the worlds largest bioethics program, which has become a model for ELSI programs around the world.,Ethical, Legal, and Social Implicat
46、ions of HGP Research,fairness in the use of genetic informationprivacy and confidentialitypsychological impact and stigmatizationgenetic testingreproductive issueseducation, standards, and quality controlcommercializationconceptual and philosophical implications,ELSI: Fairness and Privacy,Who should
47、 have access to one genetic information?How should it be used?Who owns and controls it?Consider these would-be owners: - insurers, employers, courts, schools, adoption agencies, the military,ELSI: Commercialization,property rightspatents, copyrights and trade secretsaccessibility of data and materia
48、ls,Monsanto VS. Shmeiser,ELSI: Psychological Stigmatization,How does knowing one predisposition to disease affect an individual?How does it affect friends? and family perceptions of that individual?How does it affect societys perceptions of that individual?,ELSI: Reproductive Issues,informed consent for proceduresuse of genetic information in decision makingreproductive rights,ELSI: Clinical Issues,education of health service providers, patients, and the general publicimplementation of standards and quality control measures in testing procedures,
