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TE||Sequencing the world

 一天一篇TE 2020-12-08

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全基因组测序

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Sequencing the world

测序全球

本文英文部分选自经济学人Science and Technology版块

How to map the DNA of all known plants and animal species on Earth

如何绘制地球上所有已知植物和动物物种的DNA

IN NOVEMBER 2015, 23 of biology’s bigwigs met up at the Smithsonian Institution, in Washington, DC, to plot a grandiose scheme. It had been 12 years since the publication of the complete genetic sequence of Homo sapiens. Other organisms’ genomes had been deciphered in the intervening period but the projects doing so had a piecemeal feel to them. Some were predictable one-offs, such as chickens, honey bees and rice. Some were more ambitious, such as attempts to sample vertebrate, insect and arachnid biodiversity by looking at representatives of several thousand genera within these groups, but were advancing only slowly. What was needed, the committee concluded, was a project with the scale and sweep of the original Human Genome Project. Its goal, they decided, should be to gather DNA sequences from specimens of all complex life on Earth. They decided to call it the Earth BioGenome Project (EBP).

201511月,23名生物学家在华盛顿特区的史密森学会(Smithsonian Institution)会面,策划了一项宏大的计划。自从人类的完整基因序列发表以来,已经有12年了。虽然其他一些生物的基因组也在这段时间内被破译,但这些项目对他们有一种零碎的感觉。有些基因测序是预计一次性测完的,比如鸡,蜜蜂和大米。有些基因测序更有野心,比如通过观察这些群体中几千个属的代表样品来尝试研究脊椎动物、昆虫和蛛形生物的生物多样性,但进展缓慢。委员会的结论是,我们需要的是一个具原始人类基因组计划的规模和广度的项目。他们决定,它的目标应该是从地球上所有复杂生命的标本中收集DNA序列。他们决定称之为地球生物基因组计划(EBP)

At around the same time as this meeting, a Peruvian entrepreneur living in São Paulo, Brazil, was formulating an audacious plan of his own. Juan Carlos Castilla Rubio wanted to shift the economy of the Amazon basin away from industries such as mining, logging and ranching, and towards one based on exploiting the region’s living organisms and the biological information they embody. At least twice in the past—with the businesses of rubber-tree plantations, and of blood-pressure drugs called ACE inhibitors, which are derived from snake venom—Amazonian organisms have helped create industries worth billions of dollars. Today’s explosion of biological knowledge, Mr Castilla felt, portended many more such opportunities.

与此同时,一位住在巴西圣保罗的秘鲁企业家正在制定自己的大胆计划。Juan Carlos Castilla Rubio想要将亚马逊流域的经济从采矿、伐木和牧场等产业转移到一个基于对该地区的生物及其所体现的生物信息开发利用的产业。这种转型过去至少出现过两次,橡胶树种植园的生意,以及叫做ACE抑制剂(血管紧张肽I转化酶抑制剂)的降压药,这些药物来源于亚马逊丛林的一种毒蛇。这两次转型都为该地区创造了价值数十亿美元的产业。Castilla先生认为,今天生物知识的爆炸性增长预示着更多这样的机会。

注:ACE inhibitor

https://zh./wiki/%E8%A1%80%E7%AE%A1%E7%B4%A7%E5%BC%A0%E8%82%BDI%E8%BD%AC%E5%8C%96%E9%85%B6%E6%8A%91%E5%88%B6%E5%89%82

For the shift he had in mind to happen, though, he reasoned that both those who live in the Amazon basin and those who govern it would have to share in the profits of this putative new economy. And one part of ensuring this happened would be to devise a way to stop a repetition of what occurred with rubber and ACE inhibitors—namely, their appropriation by foreign firms, without royalties or tax revenues accruing to the locals.

然而,为了实现他想要的这种转型,他认为亚马逊流域的居民和管理它的人,都必须分享这一假定的新经济利润。确保这种情况发生的一个部分是,设计一种方法来重蹈橡胶和ACE抑制物的覆辙,即它们被外国公司侵占,而不需要向当地人支付特许权使用费或税收收入。

Such thinking is not unique to Mr Castilla. An international agreement called the Nagoya protocol already gives legal rights to the country of origin of exploited biological material. What is unique, or at least unusual, about Mr Castilla’s approach, though, is that he also understands how regulations intended to enforce such rights can get in the way of the research needed to turn knowledge into profit. To that end he has been putting his mind to the question of how to create an open library of the Amazon’s biological data (particularly DNA sequences) in a way that can also track who does what with those data, and automatically distribute part of any commercial value that results from such activities to the country of origin. He calls his idea the Amazon Bank of Codes.

Castilla先生的想法不是独一无二的。一项叫名古屋协定(Nagoya protocol)的国际条款给予那些最初开发生物材料的国家以合法的权利。Castilla先生的方法独特或不寻常的是,他同时也明白,那些用于加强此类权利的管理是如何阻碍了所需知识转化成经济效益的研究。为此,他开始思考如何用一种可以追踪谁在使用这些数据的方式创造出一个亚马逊生物数据开放图书馆的问题,并且自动分配由于原产国此类活动所带来的商业价值。他把自己的想法称之为亚马逊银行准则

名古屋协定书:联合国通过历史性的《名古屋议定书》,发展中国家和发达国家同意在未来十年内,采取"有效和紧急"行动,保护全球森林、珊瑚礁和其他濒危的生态系统,以避免失去人类赖以生存的世界生物多样性状态。

Now, under the auspices of the World Economic Forum’s annual meeting at Davos, a Swissski resort, these two ideas have come together. On January 23rd it was announced that the EBP will help collect the data to be stored in the code bank. The forum, for its part, will drum up support for the venture among the world’s panjandrums—and with luck some dosh as well.

现在,在一年一度的达沃斯(瑞士的滑雪胜地)世界经济论坛的主办下,这两种想法碰到了一起。123号,据称地球生物基因组计划(EBP)将会帮助收集数据储存在代码银行(基因数据库)。这次论坛,就其本身而言,将会为世界级大佬提供支持,幸运的话,同时也有资金支持。

Branching out

范围正在扩大

The EBP’s stated goal is to sequence, within a decade, the genomes of all 1.5m known species of eukaryotes. These are organisms that have proper nuclei in their cells—namely plants, animals, fungi and a range of single-celled organisms called protists. (It will leave it to others to sequence bacteria and archaea, the groups of organisms without proper nuclei.) The plan is to use the first three years to decipher, in detail, the DNA of a member of each eukaryotic family. Families are the taxonomic group above the genus level (foxes, for example, belong to the genus Vulpes in the family Canidae) and the eukaryotes comprise roughly 9,300 of them. The subsequent three years would be devoted to creating rougher sequences of one species from each of the 150,000 or so eukaryotic genera. The remaining species would be sequenced, in less detail still, over the final four years of the project.

地球生物基因组计划(EBP)表示,他们的目标是在十年内完成150万个已知真核生物的基因测序。含有真核细胞的有机体,换句话说,就是动植物,真菌还有许多叫原生生物的单细胞有机体。(对于那些没有真核的细菌和古生物等就需要别人来进行测序 )这项计划前三年进行破译真核细胞家族的每一个成员的DNA,这些族类在基因层面属于分类组(如狐狸在犬科中归狐属),且真核细胞大约有9300种。接下来的三年将会致力于从15万真核细胞中创造出大致的排序。剩下来的物种将会在最后四年进行粗略测序。

Vulpes:  狐属。犬科的动物在我国共有4属,即豺属(Cuon)、犬属(Canis)、貉属(Nyctereutis)、狐属(Vulpes)。狼(Canis lupus)是犬科中体形最大的一种,较家犬略大。

Canidae:犬科

That is an ambitious timetable. The first part would require deciphering more than eight genomes a day; the second almost 140; the third, about 1000. For comparison, the number of eukaryotic genomes sequenced so far is about 2500. It is not, though, the amount of sequencing involved that is the daunting part of the task. That is simply a question of buying enough sequencing machines and hiring enough technicians to run them. Rather, what is likely to slow things down is the gathering of the samples to be sequenced.

这份进度表是野心勃勃的。第一阶段,科学家每天需要破解8组基因组以上;第二阶段,每天破解近140组基因组;第三阶段,每天几乎要破解1000组。相较之下,目前真核基因组已经完成测序的共有2500组。但是,所需测序的体量并不是这个任务中最令人生畏的部分。只要购买足够的测序仪器,并雇佣足够的技术人员就能完成测序。最有可能拖后腿的反而是收集用于测序的样本。

For the sequencing, Harris Lewin, a genomicist at the University of California, Davis, who was one of the EBP’S founding spirits, estimates that extracting decent-quality genetic data from a previously unexamined species will require between 40000 and 60000 for labor, reagents and amortised machine costs. The high-grade family-level part of the project will thus clock in at about 500m.

美国加州大学戴维斯分校基因组学家哈瑞斯.莱文(Harris Lewin)是地球生物基因组(EBP)的创始人之一,他预测从未检测过的物种身上提取高质量基因数据,需要大约40000-60000美元,用于支付劳力、试剂费用,并分期偿付设备成本。因此,EBP项目中,获得科级别的优质生物基因组费用约为50亿美元。

Big sequencing centres like BGI in China, the Rockefeller University’s Genomic Resource Center in America, and the Sanger Institute in Britain, as well as a host of smaller operations, are all eager for their share of this pot. For the later, cruder, stages of the project Complete Genomics, a Californian startup bought by BGI, thinks it can bring the cost of a rough-and-ready sequence down to 100. A hand-held sequencer made by Oxford Nanopore, a British company, may be able to match that and also make the technology portable.  

大型测序中心,如中国的华大基因,美国洛克菲勒大学的基因组资源中心,英国桑格研究所,以及一大群小型测序团体,都非常希望在这个巨大市场中分到一杯羹。在地球生物基因组后期粗略性阶段,Complete Genomics(华大基因收购的一家美国加州初创企业),认为可将普通的基因测序成本降至100美元。英国Oxford Nanopore凭借手持基因测序仪有望实现这一目标,使便携式测序成为可能。

The truly daunting part of the project is the task of assembling the necessary specimens. Some of them, perhaps 500,000 species, may come from botanical gardens, zoos or places like the Simthsonian (the herbarium of which boasts 5m items, representing around 300,000 species). The rest must be collected from the field. Dr Lewin hopes the project will spur innovation in collecting and processing. This could involve technology both high(autonomous drones) and low (enlisting legions of sample-hunting citizen scientists). It does, though, sound like a multi-decade effort.

项目中真正令人崩溃的部分是收集所需的标本。其中大约有50万件标本可能来自植物园、动物园,或者是诸如史密森尼博物院这样的地方(该院有500万件植物标本,代表了将近30万个物种)。其他的要从野外采集。Lewin博士希望该项目能够在收集和处理的过程的创新,包括一些高科技(自动驾驶无人机)以及传统技术(招募大量民间标本采摘科学家)。不过听起来这项目似乎需要花上几十年的时间才能完成。

It is also an effort in danger of running into the Nagoya protocol. Permission will have to be sought from every government whose territory is sampled. That will be a bureaucratic nightmare, indeed, John Kress of the Smithsonian, another of the EBP’s founders, says many previous sequencing ventures have foundered on the rock of such permission. And that is why those running the EBP are so keen to recruit Mr Castilla and his code bank.

该项目还可能会遇到名古屋议定书的阻碍。如果要从一个国家领土之内收集标本,就需要获得国家许可。从政府手续的角度来看,这确实是个梦魇。EBP项目的另一发起人,史密森尼博物院的John Kress表示,之前许多基因排序的工作就是因为没有获得这些许可而石沉大海。这也是为什么EBP项目的参与者如此希望能够获得Castilla先生和他的基因银行的支持。

The idea of code bank is to build a database of biological information using a blockchain. Though blockchains are best known as the technology that underpins bitcoin and other crypto-currencies, they have other uses. In particular, they can be employed to create “smart contracts” that monitor and execute themselves. To obtain access to Mr Castilla’s code bank would mean entering into such a contract, which would track how the knowledge thus tapped was subsequently used. If such use was commercial, a payment would be transferred automatically to the designated owners of the downloaded data. Mr Castilla hopes for a proof-of-principle demonstration of his platform to be ready within a few months.

所谓代码银行(基因数据库),就是通过区块链建立生物信息数据库。虽然区域块链最出名的是支撑比特币(比特币底层技术是区块链)和其他秘密货币的技术,但是区块链还有其他用途。值得一提的是,区块链可以用于创建、监督并实施智能协议。要访问Castilla的代码银行,意味着要签订这样一份协议,然后会对获得的知识及后续应用进行跟踪。如果被挪作商业用途,就会自动从下载数据的拥有人账户中扣款。Castilla先生希望在接下来的几个月里完成平台的原理论证示例。

In theory, smart contracts of this sort would give governments wary of biopiracy peace of mind, while also encouraging people to experiment with the data. And genomic data are, in Mr Castilla’s vision, just the start. He sees the Amazon Bank of Codes eventually encompassing all manner of biological compounds—snake venoms of the sort used to create ACE inhibitors, for example—or even behavioural characteristics like the congestion-free movement of army-ant colonies, which has inspired algorithms for co-ordinating fleets of self-driving cars. His eventual goal is to venture beyond the Amazon itself, and combine his planned repository with similar ones in other parts of the world, creating an Earth Bank of Codes.

理论上,这种智能合约能够舒解政府部门对生物剽窃的警惕情绪,并且鼓励人们试用这些数据。Castilla 先生认为,基因组数据仅是一个开端。他预见亚马逊遗传密码银行最终包含所有种类的生物复合物用于制造ACE抑制剂的蛇毒血清。例如,又像是行军蚁群畅通不堵塞的移动行为特点,激发了自动驾驶汽车的协调车队算法。他的终极目标是勇于跃出亚马逊盆地的范围,并把其规划的信息库和世界各地的相似信息库合并起来,制造一个全球遗传密码银行。

所谓生物剽窃biopiracy),一般是指发达国家的跨国公司、研究机构以及其他有关生物产业的机构凭借其生物技术上的优势,未经资源拥有国及土著和地方社区的许可和同意,利用这些国家丰富的遗传资源和相关传统知识,在物种、粮食和医药等领域进行研究和用于商业开发,进而利用西方现行的知识产权法律体系对已开发的技术申报专利,完全不考虑资源提供国/者的利益而独自获利的行为。

Plenty needs to go right for this endeavour to succeed, concedes Dominic Waughray, who oversees public-private partnerships at the World Economic Forum. Those working on different species must agree common genome-quality standards. People need to be enticed to study hitherto neglected organisms. Countries which share biological resources (the Amazon basin, for example, is split between nine states) should ideally co-operate on common repositories. And governments must resist lobbying from vested interests in the extractive industries, keen to preserve access to land, minerals or timber, which Mr Castilla’s scheme aims ultimately to curtail.

在世界经济论坛中,Dominic Waughray 是公用事业民营化发展模式的监管人。他承认,想要这番事业成功,需要付出足够的努力。负责不同物种的工作人员必须达成一个基因组质量标准的基本共识。人们也需要被鼓动着去研究迄今被忽视的有机体。理想情况下,共享生物资源的国家(例如:亚马逊河流经九个国家)应当合作运营共有的信息库。各国政府需要抵制来自采掘业的既得利益者的游说,他们热衷于保护田地,矿产,或者木材的获取,而Castilla 先生的计划最终目标是削减这些产业。

PPP模式(英语:Public-private partnership),译作政府和社会资本合作[1]、民間參與公共建設[2]、公私合作伙伴关系[3]、公用事业市场化[4]或公用事业民营化[5]等,是公共建設的开发模式之一,由公共部门与私营部门合作提供公共建設的建設与服务,在实现公共建设功能的同时,也为私营部门带来利益。这种模式由于私营部门分担了公共部门的初期投入,可以减少政府的负债,而在世界各地广泛应用。另一方面,PPP模式亦可同時配合民间与建营运后转移模式运作。

As to the money, that is the reason for the announcement at Davos. By splashing the tie-up between the EBP and the code bank in front of many of the world’s richest people, those behind the two enterprises are not so discreetly waving their collecting tins. The EBP has already been promised $100m of the $500m required for its first phase. The code bank, meanwhile, has piqued the interest of the Brazilian and Peruvian governments.

在达沃斯的宣告是为了筹资。通过在众多的世界富豪前制造EBP和遗传密码银行携手合作的头条,这两家企业的人大张旗鼓的挥动着他们的募捐箱。EBP已经承诺在其第一阶段需要的五亿美金中投入一亿美金。与此同时,遗传密码银行也引起了巴西和秘鲁政府的兴趣。

For the participants, the rewards of success would differ. Dr Lewin, Dr Kress and their compadres would, if the EBP succeeds, be able to use the evolutionary connections between genomes to devise a definitive version of the tree of eukaryotic life. That would offer biologists what the periodic table offers chemists, namely a clear framework within which to operate. Mr Castilla, for his part, would have rewritten the rules of international trade by bringing the raw material of biotechnology into an orderly pattern of ownership. If, as many suspect, biology proves to be to future industries what physics and chemistry have been to industries past, that would be a feat of lasting value.

对于参与这个项目的人来说,成功的回报是不同的。如果EBP成功的话,Lewin博士,Kress博士和他们的同僚们,可以利用基因组之间的进化关系设计出真核生物演化树的最终版本。就像化学家有元素周期表一样,生物学家也会有一个表,即一个清晰的框架。Castilla先生得到的奖励是,他通过将生物科技的原材料转变成一种井然有序的所有权模式,改写了国际贸易的法则。就如物理和化学在过去的产业发展中起到了重要的作用,如果生物学能有助于未来产业的发展,这将会是一件影响深远,长久的功绩。

翻译组:

Frank,男,小研,经济学人爱好者

Jane,女,卫生民工,经济学人爱好者

Minjia,女,广告策划,经济学人读者

Joel,男,产品运营,科技类外刊爱好者

Yifei:女,英专硕士,专八,catti二笔

校核组:

Xingyi,男,小硕,经济学人爱好者

Vambie,女,互联网民工,经济学人爱好者

3

观点 |评论|思考

关于基因测序上次在精准医疗一文中TE||Personalized medicine,小编在感想部分中有大概提到过,毋庸置疑,基因测序的发展在医疗领域将带来翻天覆地的变化。

小编今天想扯一下文中提到的“地球生物基因组计划(EBP)”,即对地球上的所有生命进行测序,其实文中也提到了几个困难,第一就是生物多样性问题,需要很多国家一起参与进来并互相合作;二是有机体样本的采集是一个特别艰难的过程,而且样本标准必须全球统一,这都需要耗费很大成本。

文后有一段评论也从另一个侧面说明了,样本的采取需要花费大量的金钱,具体如下:

Ethiopia won't allow its Coffee varieties to be examined. Similar rules abound Worldwide. Governmentsin lesser developed countries are going to demand elaborate legal compensation schemes for resulting useful products or saleable knowledge derived from "their" genomes. We may need a New International Accord to get this project on sound footing.

埃塞俄比亚不允许对其咖啡品种进行检测。而且类似的规则全世界比比皆是。欠发达国家的政府将会要求制定详尽的法律补偿方案,以获得有用的产品或从“他们”的基因组中获得的畅销的知识。我们可能需要一项新的国际协议来让这个项目建立在坚实的基础上。

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英文部分转自《经济学人》,非商业用途,仅限于小组学习,如有任何翻译错误,请大家留言更正,谢谢!

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