《自然》：2011年的诺贝尔奖应该颁给...

译者 菜鸭王

It is time that the tremendous contribution made by Carl Woese to microbiology, medicine and biology as a whole is rewarded by the Nobel committee.

    诺贝尔奖评选委员会是时候考虑卡尔伍斯对微生物学，医学和生物学做出的巨大贡献了。

Among microbiologists, Carl Woese's achievements are well known. His most lauded accomplishments include the recognition of an entirely new domain of organisms, the Archaea(Ref.1), and the subsequent introduction of the three-domain phylogeny(Ref.2) that is now widely recognized as the most accurate reflection of the relatedness of all organisms. We are so used to using neatly organized taxonomic trees to demonstrate the relationships between different microorganisms that it is easy to forget that not so long ago the classification of bacteria was considered hopeless. In 1963 Roger Stanier, then one of the foremost researchers in the field of bacterial classification, proclaimed that “The ultimate scientific goal of biological classification cannot be achieved in the case of bacteria” (Ref. 3). At that time, the classification of organisms relied on shared phenotypes, but bacteria often have too few to allow clear categorization on this basis. It was Woese who first suggested that genetic information, and in particular the sequence of the 16S ribosomal RNA gene (which had been shown previously to be highly conserved), could be used to classify organisms. 16S rRNA analysis revealed that the methanogens, which Woese investigated at the suggestion of his colleague Ralph Wolfe, are not related to any known bacteria, and this was the first step in the discovery of the Archaea(Ref.1). Ultimately, Woese demonstrated that all cellular life can be divided into three domains — Bacteria, Archaea and Eukarya — a tremendous shift from the five-kingdom classification that was prevalent previously.

　　在微生物学界，卡尔伍斯的成就无人不晓。他最为人称道的贡献包括发现了人们起初完全不知道的一类生物，古细菌(Ref.1)，紧接着又引入了物种三域分类系统(Ref.2)，现已被视作最能准确反映物种关联度的分类方法。我们都习惯于用简明扼要的分类树来演示不同微生物的亲缘关系以至于都忘了不久前我们还认为给细菌分类是件不可能的事情。1963年当时在细菌分类学上最有威望的学者Roger Stanier声称“给细菌分类的目标根本无法达到” (Ref. 3)。那时候物种分类依赖于共有的表型，然而细菌的共有表型太少无法分类。是伍斯第一个提出可以用遗传信息，特别是根据16S rRNA 的基因序列（之前已被证明高度保守）来给生物分类。在同事Ralph Wolfe的建议下，伍斯通过比对16S rRNA序列发现甲烷生成菌和任何已知的细菌都没有亲缘关系，从此揭开了古细菌的神秘面纱(Ref.1)。最终，伍斯证明世界上所有的生命都可以被分成三类——细菌，古细菌，真核生物——相比于之前流行的五类学说，这是个巨大的转变。

"Carl Woese has completely changed the way we view the relationships between all organisms on Earth"

    “卡尔伍斯颠覆了我们之前对地球上所有不同物种亲缘关系的看法。”

Carl Woese's accomplishments have been recognized by various organizations worldwide, and his awards include a MacArthur Foundation grant, the prestigious Leeuwenhoek medal (awarded by the Dutch Royal Academy of Sciences) and election to the US National Academy of Sciences. However, one prize that he has not been awarded, despite receiving several nominations, is the Nobel Prize. In part, this reflects the fact that his accomplishments may seem to be a difficult fit for the prize in physiology or medicine (and even more so for the prizes in physics and chemistry). Indeed, there are no known pathogenic archaea, and the biggest initial benefit of 16S rRNA-based phylogenetic analysis was seen in microbial ecology, as it allowed many unculturable organisms to be identified through sequencing alone. However, 16S rRNA-based phylogenetic trees are increasingly leading to advances in medicine, primarily in two ways. First, direct sequencing of the 16S rRNA genes in patient isolates can allow rapid disease diagnosis. As culturing is not required, sequence analysis can be used to diagnose many different infectious diseases and is now common in clinical diagnostic laboratories. In the case of Whipple's disease, it even led to the identification of a previously unknown bacterium (Tropheryma whipplei) as the cause(Ref.4). Second, using 16S rRNA-based phylogeny, it is possible to study the human microbiota at a detailed level. In recent years, we have begun to obtain a comprehensive picture of the composition of the human-associated microbiota in various niches, including the gut, skin and oral cavity. This has led to the insight that shifts in the gut-associated microbiota are associated with diseases such as Crohn's disease and inflammatory bowel disease, and has allowed us to study how the gut microbiota changes during ageing and in response to eating or antibiotics. We are only at the beginning of our investigations into the human-associated microbiota, but it is already clear that these organisms play a crucial part in our health and well-being. In the future, an improved understanding of the microbiota may allow us to diagnose diseases on the basis of microbiota composition and to design specific interventions.

　　卡尔伍斯的成就被世界上许多机构认可，所获奖项包括麦克阿瑟奖，享有盛誉的列文虎克奖（荷兰皇家科学院颁发）和美国科学院院士头衔。然而，有一个奖他却没有拿过，尽管获得多次提名，那就是诺贝尔奖。某种程度上，这是由于无法将其成就归类于生理学奖还是医学奖（物理学奖和化学奖就更难分得清了）。我们确实还没有发现致病的古细菌，16S rRNA 序列比较法最一开始被用于微生物生态学，因为只要测一下序就可以把很多没法培养的微生物鉴别出来。不过基于16S rRNA序列的分类树却对医学的贡献越来越大，主要体现在两个方面。第一，直接对病人提取物的16S rRNA基因测序可以实现疾病的快速诊断。由于不需要对细菌进行培养，测序技术被实验室广泛采用，用于不同传染病的临床诊断。比如在研究惠普尔氏病的时候，就发现了之前不知道的致病细菌Tropheryma whipplei(Ref.4)。第二，基于16S rRNA序列的分类法，我们才可能更加细致地研究人类微生物群。近年来，我们开始看到生活于人体不同部位包括肠道，皮肤，口腔的微生物群的全貌。我们因而能系统研究克罗恩病和肠炎对肠道细菌的影响；也让我们得以研究衰老，饮食或者抗生素对肠道细菌的影响。这方面的研究刚刚起步，不过这些生物对我们健康和幸福的重要性大家早已经很清楚了。基于对它们的更多了解，未来我们才有可能根据微生物群的组成来诊断疾病和开发有针对性的药物。

Carl Woese has completely changed the way we view the relationships between all organisms on Earth, revealed the presence of a previously unrecognized domain and provided us with a tool that has begun to elucidate the complex composition of the human microbiome, which constitutes 90% of the genetic diversity of our bodies and has been called the second human genome(Ref.5). It is difficult to think of more-fundamental discoveries that are affecting the way we think about the environment and human health alike. As the attentions of the scientific community turn once again to the decisions of the Nobel committee, perhaps it is time to campaign for Carl Woese to receive the recognition that he deserves.

　　卡尔伍斯颠覆了我们之前对地球上所有不同物种亲缘关系的看法，发现了之前不为人知的生物域，给我们提供了弄清人类微生物群复杂组成的方法，要知道人类微生物群构成了我们人体90%的遗传多样性并且已经被称为人类第二基因组(Ref.5)。很难想象还有哪个更加基础的研究像这样改变了我们对整个环境和健康的认识。科学家们再一次把目光放在诺贝尔奖评选委员会的身上，也许是时候为卡尔伍斯获得他应得的诺贝尔奖摇旗呐喊了。

References

参考文献

1.Woese, C. R. & Fox, G. E. Phylogenetic structure of the prokaryotic domain: the primary kingdoms. Proc. Natl Acad. Sci. USA 74, 5088–5090 (1977).

2.Woese, C. R., Kandler, O. & Wheelis, M. L., Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc. Natl Acad. Sci. 87, 4576–4579 (1990).

3.Stanier, R. Y., Doudoroff, M. & Adelberg, E. A. The Microbial World 2nd edn (Prentice-Hall, Englewood Cliffs, 1963).

4.Relman, D. A., Schmidt, T. M., MacDermott, R. P. and, Falkow, S. Identification of the uncultured bacillus of Whipple's disease. N. Engl. J. Med. 327, 293–301 (1992).

5.Relman, D. A. & Falkow, S. The meaning and impact of the human genome sequence for microbiology. Trends Microbiol. 9, 206–208 (2001).