生物技术发展及其对《禁止生物武器公约》的影响（中英对照）

中国代表团向《禁止生物武器公约》2012年专家会提交的工作文件：生物技术发展及其对《禁止生物武器公约》的影响<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

Working Paper submitted by Chinese Delegation to 2012 Meeting of Experts of BWC: The Effect/Impact of Biotechnology Progress on BWC

　　近年来，生物技术发展迅速，合成生物学、基因组学、系统生物学以及使能技术等领域的发展尤为引人注目。这些发展一方面极大地促进了生命科学的进步，对揭示相关疾病的致病机理和制定有效防治措施具有重要意义；另一方面其负面效应也日益凸显，产生了新的风险与挑战。

During the recent years, biotechnology has made great advances. The development in some areas, such as synthetic biology, genomics, systematic biology and enabling technologies, is especially noticeable. On one hand, these developments have greatly promoted the improvement of biological sciences, which is of great importance for the elucidation of molecular mechanisms of relevant diseases and design of efficient prevention and treatment measures. On the other hand, these developments have created new challenges and risks, and the negative effects have become more obvious.

　　一、合成生物学

1. Synthetic biology

　　合成生物学研究取得了巨大发展，从单一基因到完整代谢通路、整条染色体的合成，并形成具有完全生命特质的微生物已成为现实。由于它对人类生命健康、社会经济及环境等的潜在贡献及其可能谬用所产生的安全风险，合成生物学的发展受到极大关注。目前利用合成生物学手段，已经成功构建、合成大量标准DNA调控元件或“模块”，利用这些标准元件进一步构建可以实现特定功能的完整遗传调控网络或通路。利用合成生物学技术，在酵母中实现萜类化合物生物合成，用以生产抗疟药物前体青蒿酸，即是利用合成生物学技术发展新型抗微生物药物、促进人类生命健康的一个典型例子。2010年完整细菌基因组的合成、其在已经去除基因组的“空壳”细胞中的成功复制并导致全新细菌类型的出现，是合成生物学发展的重大事件。

From the synthesis of a single gene, single pathway, single chromosome to the totally chemical synthesis of the whole microbiological genome with life features, synthetic biology has made remarkable progress. Due to its impact on human health, social and economic development, and even the environment, as well as its potential risks of misuse, the development of synthetic biology is attracting much attention.

At present, the diverse standard DNA regulatory elements or modules have been designed, synthesized and deposited, which can be further combined to construct whole pathways, complex genetic networks with special functions. The artificial design and reconstruction of terpenoid synthesis pathways and biological production of Artesunate acid, the precursor of antimalarial drug in yeast are cases of typical successful application of synthetic biology to the green production of medical drugs to facilitate the human health.

Creation of a new form of bacterial cell controlled by a totally chemically synthesized genome which was transferred to a genome DNA repelled “empty cell” is a great event during synthetic biology development.

　　近年来作为合成生物学支撑的高通量 DNA合成技术的迅速发展，进一步降低了合成生物学的技术“门槛”，使DNA合成变得更加快捷、便宜和高效，其被谬用的风险也越来越大。

The rapid advancement of high-throughput DNA synthesis has greatly reduced the technical “bottle neck” of synthetic biology. As DNA synthesis becomes faster, cheaper and more efficient, the risks of its misuse are greatly increased.

　　自动化的DNA高通量合成与组装，一方面大大提高了不同国家获得相关研究材料的机率，同时也为有效监控提供了一定可能。可以通过建立与病原微生物DNA数据库相联的合成订单筛选系统，对不同客户提供的订单进行后台分级管理，对那些与病原微生物DNA相关的合成及其后续工作，实现全过程有效监控。

The high throughput/automatic DNA chemical synthesis and assembly have greatly facilitated the availability of research materials of different countries, while providing a good opportunity for the efficient monitoring and control of DNA synthesis. By establishing commercial order sorting, filtering and differential authorizing website administration system connected to the central pathogenic microbiology genome database, the whole process of researches related to pathogenic microbes can be efficiently monitored and controlled.

　　二、基因组学

2. Genomics

　　自从2003年完成首个人类基因组全测序以来，基因组学发展迅速，各种大规模基因组测序计划如千人基因组计划、地球微生物组计划（the Earth Microbiome Project）等也相继开展。千人基因组计划等相关研究迅速发展，使大量人群特异性遗传变异及其生物学功能得到确定，而人类特异性遗传变异与某些传染性疾病易感性之间的关系也相继得到证实。这为利用合成生物学、反向遗传学、基因组体外定向进化等手段，对整个病原微生物进行基因组的定向改造，提高致病性、传染性、宿主特异性等提供了理论和现实可行性。最近人为改造高致病性H5N1禽流感病毒传染性和宿主特异性获得成功，提示相关研究被谬用的现实可能性大大提高。

Ever since the Human Genome Project was completed in 2003, relevant researches are developing rapidly. Different large-scale genome projects, such as 1000 Genomes Projects, the Earth Microbiome Project, are under way.

While the results of 1000 Genomes Project and other relevant researches have revealed diverse human population specific genetic variations and associated functions, the GWAS (Genome-wide association study) has strongly indicated that the population-specific genetic variation is related to disease sensitivity. The confirmation of the correlation between genetic variation and disease sensitivity makes it possible to improve the specific microbes' pathogenicity, infectivity, and host specificity using combinatorial approaches of synthetic biology, reverse genetics and whole genome in vitro directed evolution.

Recently, the successful change of the infectivity and host specificity of high pathogenic H5N1 avian influenza suggests that the potential and practical risks of misuse of relevant researches are increasing.

　　此外，在高通量测序技术的推动下，人体微生物组学也取得了重要成果，发现不同人群可能存在与饮食等外在环境、自身遗传等密切相关的人群特异性微生物组，即人体第二基因组，而且这些人群特异性微生物组与人体正常生理功能密切相关。人体正常微生物组的紊乱，必将影响人体正常生理代谢并导致疾病的出现。这为通过饮食、特定微生物等隐秘手段进行人群特异性攻击提供了另外一种可能。而纳米材料、纳米技术的进步，更为人为设计改造相关微生物的有效投放与递送提供了重要工具和手段。

Thanks to the rapid progress of high-throughput next generation sequencing, the human microbiome research has revealed that our human body is closely associated with specific microbiome or human second genome that might be highly correlated with human genetics and exogenous environment elements such as dieting. The primary results of human microbiome researches also indicate that our normal physiological functions are closely related to our second genome, whose disorder might affect normal physiological metabolism of humans and even cause illness. The strong correlation of our second genome with our physiological functions provides an alternative cryptic approach to attack human population specifically through population specific microbes, even daily dieting. The rapid development of nanomaterials and nanotechnology will also provide important tools for and approaches to efficient delivery of artificially modified and designed microbes.