CHAPTER 38 Reading ‘the Book of Life’ The Human Genome Project 第38章 阅读生命之书 人体基因组计划
Humans have about 22,000 genes (the exact number is history in the making). How do we know this? Because scientists in laboratories all over the world collaborated on the Human Genome Project. This hugely ambitious project counted our genes by using DNA sequencing, and answered a question left hanging when Crick and Watson revealed the structure of DNA. The 'sequencing' meant the position, on the chromosomes, of every one of the three billion 'base pairs' of molecules that make up our genome. That's an awful lot of molecules of adenine and thymine, cytosine and guanine arranged in their double helix in the nucleus of each of our cells.
人类大约有22000个基因（精确的数字仍在研究中）。这是怎么知道的呢？因为全世界实验室里的科学家合作进行了人类基因组计划这个工程。Crick和Watson揭示了DNA的结构，人类基因组计划这个宏大的工程通过DNA排序来计算人类基因的数量，回答这个悬而未决的问题。排序是对染色体上的30亿个组成我们基因的碱基对进行。所有的adenine, thymine, cytosine, guanine（即ATCG）在细胞核中呈现双螺旋结构，这是数量非常众多的。
If understanding DNA had given us ‘the secret of life’ ~ the Human Genome Project was about reading 'the book of life'. For that is what your genome is, the genes for everything about you, from the color of your hair to the shape of your little toe. It is also about things that cannot so easily be seen: the instructions for one fertilized egg cell to become two and then four and all the way up to a whole baby in the womb. It controls the biological programs in cells that produce proteins like the hormone insulin to regulate our blood sugar. It runs the programs for chemicals in the brain that transmit messages from one nerve to the next.
如果理解DNA会给予我们生命的奥秘，那么人类基因组工程就是阅读这本生命之书。因为这就是你的基因组，一切关于你的基因，从你头发的颜色到你小脚趾的形状。这还关系到很多不那么明显的东西：受精卵从一个到两个然后到四个然后直到在子宫里形成一整个婴儿的过程的具体指令。基因还控制着细胞生产荷尔蒙、胰岛素（可以控制人体血糖）这样的蛋白质的程序。基因还运行着人脑中将一条信息从一个神经元传到另一个神经元的化学物质程序。
The Human Genome Project began in 1990 and was supposed to be finished by 2005. But in a moment of science drama, on 26 June 2000, five years ahead of schedule, an unusual thing happened. Amid great fanfare, on live television, the President of the United States of America and the Prime Minister of Great Britain announced that the first draft of the project had been completed. They were accompanied by some of the scientists who had done the work, but the presence of these two world leaders was an indication of just how important it was to understand the genome.
人类基因组工程开始于1990年，原计划2005年结束。但在2000年6月26日，比原计划提前了5年时间，科学的戏剧时刻到来了。在一片欢闹声中，电视直播了美国总统和英国首相宣布第一个人类基因组的草图已经完成。一同参加宣布的还有完成这项工程的几位科学家，但两位世界领袖的在场说明了理解基因组是多么重要。
It would take another three years, until 2003, to produce a much better version of this book of life - filling in the big gaps and correcting most of the errors. Even so, that was two years sooner than originally planned. During the years of the project the methods and technology used by the scientists, particularly the assistance provided by computers, had also advanced.
3年后，生命之书完成了一个更好的版本，改进内容包括填补了一些空白，修正了大部分错误，即使这样也比原计划早了2年。在计划进行的期间，工程采用的方法和技术，尤其是计算机提供的帮助，都改进了许多。
The genome project had developed from decades of research that followed the discovery of DNA. After Crick and Watson's revelation in 1953, an important thing to do was to 'clone' strands of DNA, to get more of the particular part of the DNA molecule you wanted to investigate. In the 1960s molecular biologists worked out that this could be done using enzymes and bacteria. Enzymes are proteins that can do all sorts of things depending on their individual structure. They were used here to do one of their natural jobs: cutting DNA into little sections. These little sections were then inserted into bacteria in a special way. Bacteria reproduce very quickly, and as these modified bacteria reproduced they also made copies of the added sections of DNA. These copies, the clones, could then be harvested for further research. The process created a lot of excitement but it was only a beginning. Whole cells as well as bits of DNA can be cloned. A sheep called Dolly was the first mammal to be cloned from an adult sheep cell. She was born in 1996 and died in 2003. Cloning techniques continue to develop and are one of the most newsworthy areas of molecular biology research.
基因组工程是在数十年发现DNA的研究中产生的。1953年Crick和Watson发现了DNA之后，一项重要的工作就是复制其中的若干段，可能是我们需要进行研究的一些DNA分子。60年代分子生物学家通过酶和细菌完成了实验。酶是蛋白质，不同结构的酶可以做不同的工作。这里酶被用于做它们的本职工作：把DNA切成小段。这些小段的DNA通过特殊方式插入到细菌之中。细菌繁殖的非常快，当它们繁殖的时候，那些改变了的DNA也出现了很多副本。这些副本可以用作进一步的研究。这个过程中有很多令人兴奋的地方，但这只是一个开始。就像DNA片段一样，整个的细胞也可以被复制。多莉羊就是从一个成年绵羊的细胞克隆出来的，它是第一只克隆出来的哺乳动物。多莉羊1996年克隆成功，2003年死亡。克隆技术继续发展，现在仍然是最具新闻性的分子生物学研究领域。
Now that the scientists had lots of the bits of DNA to experiment with, they began to try to solve the problem of DNA sequencing: to reveal the order of the base pairs of molecules in DNA. This was a job for the English molecular biologist Frederick Sanger(b. 1918), working in Cambridge. Sanger had already won one Nobel Prize in 1958 for working out the order of the amino acids of the protein insulin.
现在科学家可以进行实验的DNA片段很多，然后就开始尝试解决DNA排序的问题：DNA中碱基对的顺序。这是在剑桥的英国分子生物学家Frederick Sanger(b.1918)的工作，他已经因为研究出胰岛素蛋白质的氨基酸顺序而在1958年获得诺贝尔奖。
One of the key differences between amino acids and DNA is that the DNA molecules are much longer, and have many, many more base pairs than proteins have amino acids. Also each amino acid is less chemically similar, whereas the DNA bases were much like each other, which makes them harder to sort out. Building on his own earlier work, and that of others, Sanger found a way to prepare short strands of DNA using radioactive labels, chemicals and enzymes. He adapted various biochemical methods to find a way of separating out the adenine, thymine, cytosine and guanine from each other. To do this, he exploited the fact that as chemical compounds they have slightly different chemical and physical properties. The best results came with a process called electrophoresis.
DNA和氨基酸的一个重要区别是DNA分子长的多，而且DNA的碱基对比蛋白质的氨基酸多的多。每种氨基酸在化学性质上不是很相似，而DNA碱基对相互之间则很像，这使排序工作更加困难。在他以及其他人前期工作的基础上，Sanger发现了一种使用放射性标签、化学物质和酶来准备DNA短片段的方法。他尝试调整了很多种生物化学方法来使ATCG相互分离。他发现ATCG作为化学上的化合物，有些略微不同的化学和物理特性。最好的结果是通过电泳（electrophoresis）的方法得到的。
To make sure the results were accurate enough, Sanger and his team processed multiple copies of each strand several times and compared the results. It was a very time-consuming, repetitive process. But by using lots of the short strands of the long molecule and then looking to see where they started and ended, they managed to match up the strands and produce a readable DNA sequence. In 1977 they had their first success in reading the genome of an organism. It was a humble one, a bacteriophage called phi X 174. Bacteriophages are viruses that infect bacteria, and phi X 174 was one often used as a tool in molecular biology laboratories. In 1980 Sanger won his second Nobel Prize for this valuable work.
为了确保结果准确度高，Sanger和他的团队将每段DNA短片都复制了几次，对比其结果。这是一个非常耗时的重复过程。通过观察很多DNA短片的起始位置，他们成功的匹配上了短片并得到了一个可读的DNA序列。1977年他们第一次成功的读取了一种微生物的基因组。这是一种简单的微生物，一种名叫phi X174的噬菌体。噬菌体是能感染细菌的病毒，phi X 174是一种经常用在分子生物实验室的工具。1980年Sanger由于这项工作赢得了第二次诺贝尔奖。
The next genome targets were also laboratory organisms. Despite how hard it was to produce a readable DNA sequence, molecular biologists carried on with their research. Meanwhile, innovations in computing helped with analyzing the patterns of the bases on the short strands. The scientists pressed on keenly. If they knew exactly which genes an organism had, and which proteins each gene could manufacture, they would be able to understand very basic things about how the organism was made, literally cell by cell from fertilized egg to adult.
下一个基因组的目标也是实验室的微生物。尽管得到一个可读的DNA序列非常困难，但分子生物学家们还是继续他们的研究。同时，计算方面的创新对分析片段上的碱基对很有帮助，科学家们非常热心的继续推进工作。如果他们知道每个生物体有什么基因，每个基因能生产什么蛋白质，他们就可以理解如何制造生物体中非常基础的东西，也就是如何一个细胞一个细胞的从受精卵到成人个体。
The fruit fly was an obvious candidate for their research. Thomas Hunt Morgan and his group had already done a lot on its inheritance patterns, and some crude gene-mapping, before 1950. Another was a tiny roundworm called Caenorhabditis elegans. At only one millimeter long, it had exactly 959 cells, including a simple nervous system. Now it might not seem like much of a pet, but C. elegans was the favorite laboratory animal of Sydney Brenner (b. 1927), and had been for many years. Brenner had come from South Africa to the Laboratory of Molecular Biology (LMB) in Cambridge in 1956. Since the 1960s he had been investigating its development, since its cells were easy to see. He thought it would be possible to determine exactly what each of the cells in the embryo worm would become in the adult. He hoped that if he could reveal the worm's genome, he would be able to relate its genes to how the adult worm carries out its living functions.
果蝇是研究的理想备选对象。1950年以前，Thomas Hunt Morgan和他的团队在果蝇的遗传模式和简单的基因定位方面做了很多工作。另一个是一种名叫Caenorhabditis elegans的很小的蛔虫。它只有一毫米长，有959个细胞，还有一个简单的神经系统。这肯定不像是什么宠物，但C. elegans却在很多年里都是Sydney Brenner(b.1927)的最喜欢的实验室生物。Brenner在1956年从南非到了剑桥的分子生物学实验室（LMB），由于其细胞很容易就观察的到，60年代他就在研究其进展。他觉得观察确定其胚胎中的每个细胞在成熟个体中成为什么是可行的，他认为如果他可以找到蛔虫的基因组，他就可以将成熟个体如何发挥作用与其基因联系起来。
In the course of their work, Brenner and his team also learned a lot about the ordinary lives of cells in an animal, including one very important job that the cell must do: die when it is time to die. Plants and animals always make new cells: think of your skin and how it rubs off when you have been in the bath a long time. We get rid of the dead stuff, and new, living cells replace it underneath. All this living and dying within an organism is a regular feature of nature, and the genes program this process. That is why cancer cells are so dangerous: they don't know when it is time to die. Trying to influence the gene that has failed to tell the cell it is time to stop dividing is a major part of modern cancer research. Brenner and two colleagues won the Nobel Prize in 2002 for their work with the lowly roundworm.
在工作的过程中，Brenner和团队也学习到了很多关于生物体中细胞的正常生活，其中包括重要的必须做的工作：当该死亡的时候，就死亡。植物和动物都在不断的制造新细胞：只要想想你的皮肤和在洗了一个澡后摩擦下来的皮肤碎屑。我们除去旧的死皮，下面新生的细胞就代替了旧的位置。一个生物体中的生存和死亡都自然界中的正常现象，基因控制着这个过程。现代癌症研究的一个主要部分就是试图影响未能成功告诉细胞停止分裂。由于低级蛔虫的工作，Brenner和两个同事获得了2002年诺贝尔奖。
By this time, one of those colleagues, John Sulston (b. 1942), was leading the British team taking part in the Human Genome Project. The project stands as a symbol of modern science. First, it was expensive and thousands of people worked on it. The modern scientist is rarely a lone worker, and it is quite normal today for scientific papers to have dozens or even hundreds of authors. The work may require many individuals with different skills. It's been a long time since William Harvey worked alone on the heart, or Lavoisier in his laboratory had his wife as his only assistant. Several laboratories worked together on sequencing the human genome. They divided up the chromosomes between them, so cooperation and trust were needed, and every lab had to produce the sequences to the same high standards. This needed many smaller portions of the DNA, and then computer analysis to fit them together in a single sequence. Running these laboratories was expensive, so generous funding was needed. In the United States it was provided by the government-supported labs at the National Institutes of Health (NIH) and elsewhere. In Britain, first government grants, and then a large private medical research charity, the Wellcome Trust, paid for the research. The French and Japanese governments funded smaller laboratories, making the project truly international.
现在，其中一个同事，John Sulston(b.1942)正在领导团队英国人类基因组工程。这项工程是现代科学的象征。首先，这项工程非常昂贵，需要数千人一起工作。现代科学家通常都不是单独工作，而且现代科学论文有数十个乃至数百个共同作者都是很正常的。这项工作具有不同技能的很多人一起。像William Harvey独自一个人研究心脏，或者Lavoisier在实验室里只有他妻子作助理，这样的时代已经过去很久了。几个实验室合作进行人体基因组排序，他们将染色体分成几段分发给每个实验室，所以需要合作与信任，每个实验室都需要得到相同的高标准的排序结果。这需要DNA的更小片段，然后用计算机分析将它们形成一个序列。这些实验室运行起来都非常昂贵，所以需要大批基金支持。在美国是由*支持的NIH的实验室和其他实验室。在英国，首先*拨款，然后由一个大的私人医疗研究福利基金会，即Wellcome基金会，出资支持研究。法国和日本*投资的小型实验室也参加了研究，使这项工程真的成为国际工程。
Second, the project - and indeed, modern science itself- would be impossible without the computer. The scientists had to analyze large amounts of information as they looked at each strand of DNA and tried to see where it began and ended. For humans, it would be overwhelming, but computers do this quickly. Many scientific projects now include people who only look after the computers and computer programs, not the fruit flies or test tubes.
第二，如果没有计算机，这项工程（实际上是现代科学）根本就不可能成功。当观察每个小段的DNA，确定在何处开始，何处结束，科学家需要分析大量信息。对于人类来说，这项工程太浩大了，但计算机可以轻松的完成这项工作。许多科学工程现在都包括哪些只维护计算机和计算机程序的人，而不是维护果蝇或试管的。
Third, modern science is big business, with a lot of money to be made as well as spent. The Human Genome Project became a race between the publicly funded groups and a private company established by the American entrepreneur Craig Venter (b. 1946). Venter, a gifted scientist, helped develop some of the equipment that could speed up DNA sequencing. He wanted to be the first to decode the human genome, patent his knowledge and charge scientists and pharmaceutical companies to use his information. The final result was a compromise. The whole human genome is freely available, but some of the ways that this information can be used can be patented, and the resulting drugs or diagnostic tests can be sold for profit. And, of course, people today pay to have their DNA sequenced, hoping that what they learn will help them maintain their health and avoid diseases that might affect them in the future.
第三，现代科学就像是大规模的生意一样，有大量的资金投入和产出。人类基因组工程成为了一场公共投资与私人公司投资（美国企业家Craig Venter，1946年出生）的竞赛。Venter是一个有天赋的科学家，他开发出了一些可以加速DNA排序的设备。他希望成为第一个解码人类基因组的人，将之注册专利，并向使用其专利信息的科学家和药企收费。最后的结果是一个折中，人类基因组信息是免费的，但使用这些信息的一些途径是可以注册专利的，通过这些途径制成的药品或诊断实验可以出售。当然，现在人们可以付费得到自己的DNA序列，希望这些知识能够在将来保证他们的健康，避免疾病。
Finally, the genome project is a telling example of the 'hype' surrounding today's important science. Scientists must compete for scarce funds, and sometimes exaggerate the significance of their research to get their grants. Journalists cover their stories, putting the most dramatic gloss they can on them, since ordinary science is not news. Each fresh announcement of a discovery or breakthrough raises the public's expectations that a cure or treatment is just around the corner. But mostly science takes longer for its lasting effects to be realized. New knowledge is gained every day, and new therapies are regularly introduced. But most science advances little by little, and media hype is rarely spot-on.
最后，基因组工程是现代重要科学中大肆宣传的典型例子。科学家需要竞争得到稀缺的投资，有时候需要夸大其研究的重要性来得到拨款。由于普通的科学已经不是新闻，记者们需要将它带上最神奇的光环放到封面故事上才可以。每新发布一个发现或突破，都会提高公众的期望，觉得治疗办法已经就在眼前了。但大多数科学需要更长的时间才能产生效果。每天都会得到新知识，新的疗法定期介绍出来，但大多数科学总是一点一点缓慢的进步，媒体宣传很少能报道到点子上。
Yet it is a huge achievement to be able to read the human genome, because it can give us a much more precise understanding of health and disease. It will, in time, help us to develop new drugs against cancer, heart disease, diabetes, dementia and the other killers of modern times. We all stand to lead healthier lives as a result of this important work, involving scientists in many fields and many countries.
但能读到人类基因组还是一个巨大的成功，因为这可以使我们对健康和疾病有更精确的理解。最后，它肯定会帮助我们研制出新药来抵抗癌症、心脏病、糖尿病和其他现代杀手。这项涉及到众多领域的科学家与许多国家的工作，肯定会使我们的生活方式更加健康。