2 走进生命生命秘密一(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 数月前，比尔·克林顿和托尼·布莱尔联合宣布了科学史上最伟大的成就之一：解秘人 类基因组或曰“生命之书”。2月份，科学家们首次一览实验证据，在《自然》和《科学》两杂 志上发表了官方的人类基因组序列论文。 　　两家旗鼓相当的测序对手机构——公共人类基因组计划和美国生物技术赛莱拉公司—— 完成了大量的科学论文。他们给出的最令人惊讶的结论是：人类拥有的基因数那么少， 只不过3万个左右。这与小鼠的基因数目相当，是果蝇或线虫基因数目的两倍。绝大多数 科学家预测人有10万个基因，有的科学家则估计达14万个。 　　美国怀特海德基因组研究中心主任埃里克·兰德说：“这么少的基因数目对人类的尊 严似乎是某种冒犯啊。” 　　生物学家将不得不放弃单个基因给机体发指令制造单一蛋白质的学说(像激素和酶这 些控制生物学过程的分子都是蛋白质)。代之的是，我们必须把人类全部DNA——基因组—— 看作是一个极为复杂的系统。 　　正如赛莱拉总裁克雷格·温特所说的那样，“基因无所谓‘好’、‘坏’，只存在着不同 层次、不同联系的网络活动，以及对干扰作出反应的敏感程度的不同。一个基因等于一 种疾病，或说一个基因制造一种关键性的蛋白质的学说，已被彻底否定。” 　　没有一个人能说出究竟有多少蛋白质。这个问题的答案需要等上几年，由新兴的蛋 白质学告诉我们。蛋白质学是继基因组学之后即将出现的新学科。但是，温特博士估计 人类有25万种不同的蛋白质，也就是说每一个基因负责大约10个蛋白质，从而执行人体 内的基本任务。 　　一些专家说，未料到人类基因数目如此少，但这对医学可能是个好消息，因为这样 需要弄明白的基因就较少。不好的是，从相反的角度来看，它们也会发挥同样的功能， 即基因间的复杂相互作用有可能对像利用基因疗法中改变一、两个基因就能治病的过程 带来更大的困难。但这也有可能部分地解释了为什么基因疗法在过去十多年的临床实践 中一直给出令人失望的结果。而新兴的干细胞技术用有潜能的新细胞替代失去功能的细 胞，有可能产生更理想的结果，因为病人一下子接受到的是全部完整的遗传系统。 　　2月发表的基因组是混合序列，它们来自赛莱拉的五个自愿者和公共计划组十来个人 。他们代表着所有的主要人种群体。其结果表明，来自两个不相干个体的DNA有99.9％相 同，平均起来看，在他们遗传密码的30亿个化学“字母”中大约有300万个不相同。按温特 博士的观点，真正的生物学差异还要远低于这个数字。在人类遗传密码中的变异大多数 没有功效，他预计“在不 相关的人中只不过有大约10万个遗传密码的差异有生物学意义。” 　　发现DNA差异是人类基因组工程未完成工作的最重要的一个部分。例如，这可能是药 物基因组学的基础，也就理解了为什么患某种特殊疾病的某些人比另一些人对某种药物 治疗反应好的原因。 　　研究工作的另一途径是把人类基因组与其他动物的做详细对比。它们间的差异将会 帮助我们揭开基因多种功能。同时，技术专家们正在忙着降低DNA测序成本，即个人基因 组可以在基因芯片上按程序读出。哈佛大学利佩尔计算遗传学中心主任乔治·丘奇指出， 将来一个人的基因组的信息是可以存放在计算机DVD盘里。 1.linkup联合在一起 2.proclaim[πρΕ5κλειμ]vt.宣布，宣告 3.genome[ 5δ
2 走进生命生命秘密一(doc)