2 走進生命生命秘密一(doc)
2. A glimpse of the secrets of Life Several months ago, Bill Clinton and Tony Blair linked up1 to proclaim2 one of science's greatest achievements:decoding the human genome3 or “ book of life” . In February scientists get their first look at the evidence, with the official publication4 of the human genome sequence5 in the journals6 Nature and Science. 　　The two rival7 sequencing organizations--the Public Human Genome Project and Celera, the US biotechnology company--have produced scores8 of scientific papers. Their most striking9 conclusion is how few genes we have: around 30,000. That is about the same number as a mouse and only twice as many as a fruit fly or a worm. Most scientists had expected to find about 100,000 human genes and some estimates ran to10 140,000 genes. Eric Lander, director of the Whitehead Centre for Genome Research in the US, says: “ It seems to be some kind of affront11 to human dignity12.” 　　Biologists will have to stop thinking of individual genes giving the body instructions to make individual proteins13 (proteins are the molecules14 such as hormones15 and enzymes16 that control biological processes). Instead, all our DNA--the genome--must be seen as one immensely complex system. 　　As Craig Venter, president of Celera, puts it, “ There are no ‘ good’ genes or ‘ bad’ genes, merely networks that exist at various levels and various connectivities, and at different states of sensitivity to perturbation17. The notion that one gene equals one disease, or that one gene produces one key protein, is flying out of the window18.” 　　No one knows how many proteins there are. The answer will be revealed over the next few years by the emerging field of proteomics19, successor to genomics20. But Dr. Venter estimates that we have 250,000 different proteins--about 10 for every gene--to do the essential work in our bodies. 　　Some experts were saying that the unexpectedly low number of human genes would be good for medicine, since there are fewer genes to understand. But it could work equally well in the opposite direction: the complex interactions between genes may make it harder to cure disease by changing one or two of them, for example through gene therapy. This may explain partly why gene therapy has given disappointing results in clinical trials over the past 10 years. The emerging technology of stem cells replacing failing cells with potent new cells--may produce better results because the patient is receiving the whole genetic system at once. 　　The genomes published in February are composite sequences, derived from five volunteers in the case of Celera and a dozen people for the public project. All the main racial groups21 are represented. The results show that DNA from two unrelated individuals is 99.9 percent identical-- on average, about 3m of the 3bn chemical ‘ letters’ in their genetic code will be different. But the real biological differences are far less even than this figure would suggest, according to Dr. Venter. The majority of variations in the human genetic code have no effect and “ only about 10,000 genetic differences between unrelated humans will be biologically significant,” he predicts22. 　　Discovering the DNA differences that matter is one of the most important pieces of unfinished business for the human genome project. It will be the basis, for example, of pharmacogenomics23--understanding why some people with a particular disease respond better than others to drug treatment. 　　Another important avenue24 of research will be to compare the human genome in detail with other animals. Differences will help to reveal the functions of the genes. Meanwhile, technologists are working to drive down25 the costs of DNA sequencing so individual human genomes can routinely be read out on gene chips26. George Church, director of the Lipper Centre for Computational Genetics at Harvard, points out that the information content of an individual genome can fit on a computer DVD disk. 生命秘密一瞥 數(shù)月前，比爾·克林頓和托尼·布萊爾聯(lián)合宣布了科學(xué)史上最偉大的成就之一：解秘人 類基因組或曰“生命之書”。2月份，科學(xué)家們首次一覽實驗證據(jù)，在《自然》和《科學(xué)》兩雜 志上發(fā)表了官方的人類基因組序列論文。 　　兩家旗鼓相當?shù)臏y序?qū)κ謾C構(gòu)——公共人類基因組計劃和美國生物技術(shù)賽萊拉公司—— 完成了大量的科學(xué)論文。他們給出的最令人驚訝的結(jié)論是：人類擁有的基因數(shù)那么少， 只不過3萬個左右。這與小鼠的基因數(shù)目相當，是果蠅或線蟲基因數(shù)目的兩倍。絕大多數(shù) 科學(xué)家預(yù)測人有10萬個基因，有的科學(xué)家則估計達14萬個。 　　美國懷特海德基因組研究中心主任埃里克·蘭德說：“這么少的基因數(shù)目對人類的尊 嚴似乎是某種冒犯啊。” 　　生物學(xué)家將不得不放棄單個基因給機體發(fā)指令制造單一蛋白質(zhì)的學(xué)說(像激素和酶這 些控制生物學(xué)過程的分子都是蛋白質(zhì))。代之的是，我們必須把人類全部DNA——基因組—— 看作是一個極為復(fù)雜的系統(tǒng)。 　　正如賽萊拉總裁克雷格·溫特所說的那樣，“基因無所謂‘好’、‘壞’，只存在著不同 層次、不同聯(lián)系的網(wǎng)絡(luò)活動，以及對干擾作出反應(yīng)的敏感程度的不同。一個基因等于一 種疾病，或說一個基因制造一種關(guān)鍵性的蛋白質(zhì)的學(xué)說，已被徹底否定。” 　　沒有一個人能說出究竟有多少蛋白質(zhì)。這個問題的答案需要等上幾年，由新興的蛋 白質(zhì)學(xué)告訴我們。蛋白質(zhì)學(xué)是繼基因組學(xué)之后即將出現(xiàn)的新學(xué)科。但是，溫特博士估計 人類有25萬種不同的蛋白質(zhì)，也就是說每一個基因負責大約10個蛋白質(zhì)，從而執(zhí)行人體 內(nèi)的基本任務(wù)。 　　一些專家說，未料到人類基因數(shù)目如此少，但這對醫(yī)學(xué)可能是個好消息，因為這樣 需要弄明白的基因就較少。不好的是，從相反的角度來看，它們也會發(fā)揮同樣的功能， 即基因間的復(fù)雜相互作用有可能對像利用基因療法中改變一、兩個基因就能治病的過程 帶來更大的困難。但這也有可能部分地解釋了為什么基因療法在過去十多年的臨床實踐 中一直給出令人失望的結(jié)果。而新興的干細胞技術(shù)用有潛能的新細胞替代失去功能的細 胞，有可能產(chǎn)生更理想的結(jié)果，因為病人一下子接受到的是全部完整的遺傳系統(tǒng)。 　　2月發(fā)表的基因組是混合序列，它們來自賽萊拉的五個自愿者和公共計劃組十來個人 。他們代表著所有的主要人種群體。其結(jié)果表明，來自兩個不相干個體的DNA有99.9％相 同，平均起來看，在他們遺傳密碼的30億個化學(xué)“字母”中大約有300萬個不相同。按溫特 博士的觀點，真正的生物學(xué)差異還要遠低于這個數(shù)字。在人類遺傳密碼中的變異大多數(shù) 沒有功效，他預(yù)計“在不 相關(guān)的人中只不過有大約10萬個遺傳密碼的差異有生物學(xué)意義?！?　　發(fā)現(xiàn)DNA差異是人類基因組工程未完成工作的最重要的一個部分。例如，這可能是藥 物基因組學(xué)的基礎(chǔ)，也就理解了為什么患某種特殊疾病的某些人比另一些人對某種藥物 治療反應(yīng)好的原因。 　　研究工作的另一途徑是把人類基因組與其他動物的做詳細對比。它們間的差異將會 幫助我們揭開基因多種功能。同時，技術(shù)專家們正在忙著降低DNA測序成本，即個人基因 組可以在基因芯片上按程序讀出。哈佛大學(xué)利佩爾計算遺傳學(xué)中心主任喬治·丘奇指出， 將來一個人的基因組的信息是可以存放在計算機DVD盤里。 1.linkup聯(lián)合在一起 2.proclaim[πρΕ5κλειμ]vt.宣布，宣告 3.genome[ 5δ
2 走進生命生命秘密一(doc)