Science12月17日公布了2010年十大科学突破，其中合成生物学、尼安德特人基因组、HIV预防等一系列热点均包含在内，但是热门的砷基生命并没有入选。

冠军：量子机械

在今年之前，所有的人造物体的移动都遵循经典力学的法则。然而，在今年3月，一组研究人员设计了一种精巧的装置，其运动方式只能够用量子力学来描述（量子力学是一组支配如分子、原子及亚原子颗粒等细小物体运行的法则）。为了表彰他们的实验在概念上的拓展、其独创性以及它的众多的潜在用途，Science杂志称这一发现是2010年最重大的科学进展。

加州大学圣巴巴拉分校的物理学家Andrew Cleland 与John Martinis设计了这一机械：一个人们可用肉眼看到的极其细小的金属半导体桨状物，并巧妙地使它按照量子规范舞蹈。首先，研究人员将该浆状物冷却至其“基态”（即量子力学所允许的最低能态，这是物理学家长期以来所追求的目标）。他们接着将该装置的能量提高一个量子以产生一种纯粹的量子力学的运动状态。他们甚至设法将该装置同时进入到两种能态，因此该装置在同一时间会有微小的振动及很大的振动，这种奇怪的现象在量子力学的奇怪法则中是允许出现的。

Science杂志及其发行机构——美国科学促进会（AAAS）认为，这一首创的量子机械是2010年的年度突破。它们还将过去的这一年中的另外9个重要的科学成就汇编成今年的10大科学成就，该榜单出现在Science杂志2010年12月17日刊的一个新闻专版中。

Science杂志的一名新闻作者Adrian Cho说：“今年的年度突破所代表的是科学家们第一次在一种人造物体的运动中示范了量子效应。这在概念层次上来说非常酷，因为它将量子力学扩展到了一个全新的领域之中。在实用的层面上，它开启了多种可能性：从将光量子调控以及电流和运动相融合的新实验到也许某一天人们可以测试量子力学的界限以及我们的现实感。”

量子机械证明，量子力学原理适用于大到肉眼可见的物体的运动以及原子和亚原子颗粒的运动。它为人们朝着在量子水平获取对一种物体的振动的完全控制的方向迈出了关键性的第一步。这种对某种人造装置的运动控制将允许科学家们操控那些极小的运动，这很像他们现在对电流和光粒子的控制。这种能力转而可能会导致控制光量子态、超敏感力探测器等新装置的出现以及最终的对量子力学的界限和我们的现实感的研究。（最后的这一宏伟目标可以通过尝试将一个肉眼可见的物体放入到一个能态中来完成；在这一能态中，该物体可同时直接处于2个略微不同的地方——这一实验可准确地披露为什么大到像人这样的物体不可能同时出现在两个地方。）

Cho说：“请注意，物理学家还没有达到让一个像这样细小的物体同时出现在两个地方的境界。但现在他们已经进入到量子运动的最简单的状态；看来做到它要比过去容易得多了：这更像是一个‘什么时候可做到’而不是‘是否能做到’的问题。”

其它9大开创性成就的名录如下：

合成生物学：在生物学和生物技术的一个决定性时刻，研究人员构建了一个合成的基因组，并用它转变了一种细菌的身份特性。该基因组取代了该细菌的DNA，使其生产出一组新的蛋白质——这一成就促使国会对合成生物学召开了一个听证会。研究人员预计，将来，定制的合成基因组可用来产生生物燃料、医药品或其它有用的化学制品。

人造生命专题-生物谷生物研究频道
Science：世界首个人工生命结构诞生
Science：RNA可改变细胞转导通路的线路
PNAS：small RNAs选择性杀伤癌症细胞
生物谷评论：人工生命能否真正实现？
人造细胞后的生命——Nature专访八位合成生物领域专家
“人造生命”：超越自然还是带来毁灭
生物谷张 发 宝博士：影响人类未来的十大生物科学技术

Build Your Own Genome

A technical tour de force grabbed headlines around the world for synthetic biology this year. In what was hailed as a defining moment for biology and for biotechnology, researchers at the J. Craig Venter Institute (JCVI) in Rockville, Maryland, and San Diego, California, built a synthetic genome and inserted it into a bacterium in place of the organism's original DNA. The new genome caused the bacterium to produce a new set of proteins.

The synthetic genome was an almost identical copy of a natural genome, but ultimately, researchers envision synthetic genomes custom-designed to produce biofuels, pharmaceuticals, or other useful chemicals. Also this year, researchers at Harvard University improved their high-throughput method of modifying existing genomes for such purposes, and other synthetic biologists showed that RNA-based “switches” can get cells to behave differently in response to certain signals.

J. Craig Venter and his team built its $40 million genome from smaller pieces of store-bought DNA. First they stitched the synthetic DNA together in stages in yeast; then they transplanted it into a bacterium, where it replaced the native genome.

Although not truly “artificial life,” as some media declared, this success prompted a congressional hearing and a review by a presidential commission on the ethics of synthetic biology.

It's far from the only synthetic biology game in town, however. In 2009, Harvard's George Church introduced a technique called multiplex genome engineering, which adds multiple strands of DNA to bacteria every couple of hours, rapidly generating genetically engineered organisms with extensively revamped genomes. This year, his team came up with a cheaper way to produce the DNA strands used to modify the genome, in hopes of making this approach cost-effective for industrial use.

Teams led by Caltech's Niles Pierce, Stanford University's Christina Smolke, and Boston University's James Collins have come up with ways to change a cell's behavior by modifying its regulatory pathways. In some cases, they add specially designed RNA molecules that can sense molecules in the cell associated with, say, cancer or inflammation. Once that happens, they cause the cell to produce a protein that may sensitize the cell to drugs or cause it to undergo programmed cell death. Another team made a riboswitch that caused bacteria to seek out and destroy the herbicide atrazine. Such devices are much closer than synthetic and modified genomes to having practical applications.

尼安德特人基因组：研究人员对在3万8000年至4万4000年前曾经生活在克罗地亚的3个女性尼安德特人的骨头做了尼安德特人的基因组测序。对DNA降解片段进行测序的新方法使得科学家们能够第一次对现代人基因组与我们的尼安德特人祖先的基因组进行直接的比较。

Science：尼安德特人的基因组序列及“目标序列捕捉”测序新技术
Science：尼安德特人的数目可能很少
Current Biology：利用第二代测序技术研究远古人类DNA

Reading the Neandertal Genome

Thirteen years ago, when researchers sequenced just a few snippets of mitochondrial DNA from a Neandertal, the breakthrough made headlines worldwide. This year, researchers published a draft of the Neandertal nuclear genome—and their first analysis of what these 3 billion bases of DNA reveal about the evolution of these extinct humans and us.

Using new methods to sequence degraded fragments of ancient DNA (see “Insights of the Decade,” p. 1616), researchers spliced together a composite sequence from three female Neandertals who lived in Croatia 38,000 to 44,000 years ago, to reconstruct about two-thirds of the entire Neandertal genome. For the first time, scientists could compare in detail the genomes of Neandertals and of modern humans.

Reading this sequence, the researchers concluded that modern Europeans and Asians—but not Africans—have inherited between 1% and 4% of their genes from Neandertals. Apparently, Neandertals interbred with modern humans after they left Africa at least 80,000 years ago but before they spread into Europe and Asia. If correct, this stunning discovery challenges a model that says that as modern humans swept out of Africa, they completely replaced archaic humans such as Neandertals without interbreeding.

The Neandertal genome also gives researchers a powerful new tool to fish for genes that have evolved recently in humans, since they split from Neandertals. The catalog includes 78 differences in genes that encode proteins that are important for wound healing, the beating of sperm flagella, and gene transcription. Several encode proteins expressed in the skin, sweat glands, and inner sheaths of hair roots, as well as skin pigmentation—all differences that reflect adaptations to new climates and environments as modern humans spread around the globe.

The researchers have also identified 15 regions of interest that differ between humans and Neandertals, including genes that are important in cognitive and skeletal development. When mutated in humans, some of these genes contribute to diseases such as schizophrenia, Down syndrome, and autism, or to skeletal abnormalities such as misshapen clavicles and a bell-shaped rib cage.

As researchers close in on the few genes that separate us from Neandertals, they are also trying to decipher how differences in genetic code alter proteins produced in the lab. This year, scientists inserted 11 pairs of single peptides into eukaryote cells to test for differences in gene expression. With luck, they may pinpoint some of the genes that equipped us to survive while Neandertals went extinct.

下一世代的基因组学：更快更廉价的测序技术使人们能够对远古和现代的DNA进行非常大规模的研究。例如，1千个基因组计划已经发现了令我们人类独一无二的基因组变异——而其它正在进行中的计划一定还会披露更多的基因组功能。

Nature：千人基因组计划发布最详尽的人类基因多态性图谱
Nat.Genetics：首份日本人基因组图谱绘制成功
Science：首个家庭基因组测绘完成
Nature：4000年前古人基因组证实黄种人从亚洲迁徙到美洲
PLoS Biology：中国人单碱基精确度的全基因组DNA甲基化图谱绘制完成

Next-Generation Genomics

Genomics researchers savored the fruits of massively parallel sequencing in 2010. Cheaper, faster “next generation” machines have taken hold over the past 5 years; this year they yielded important results from several large projects.

One ambitious effort, the 1000 Genomes Project, seeks to find all single-base differences—or single-nucleotide polymorphisms (SNPs)—present in at least 1% of humans. It completed three pilot studies this year, which together identified 15 million SNPs—including 8.5 million novel ones. The information will help scientists track down mutations that cause diseases.

Researchers also finished cataloging all the functional elements in the genomes of the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans; the results are expected to be published by year's end. In human DNA, the complete genome sequences of two Africans from hunter-gatherer tribes, the oldest known lineages of modern humans, confirmed the extensive genetic diversity within those groups. Researchers also produced a draft of the Neandertal genome (see p. 1605) and deciphered the genome from 4000-year-old hair preserved in Greenland's permafrost.

The cornucopia of results also included surveys of all the transcribed DNA—the so-called transcriptome—and of protein-DNA interactions, as well as assessments of gene expression and the identification of rare disease genes.

RNA的重新编程：重新编程细胞——即将细胞的发育时钟回拨，使其表现如胚胎中的非特异性的“干细胞”——已经成为一种研究疾病和发育的标准实验室技术。今年，研究人员找到了一种用合成RNA来做这一工作的方法。与以往的方法相比，这种新的技术的速度要快2倍，功效要高100倍，并在治疗应用上可能更为安全。

Cell：三种提高iPS细胞诱导率的蛋白
Cell Stem Cell：新方法可将人类皮肤细胞重编程为干细胞
PLoS ONE：羊水细胞重编程为iPS细胞
一种高效诱导体细胞重编程的方法-
Nature：胸腺细胞的重新编程
2010年度国内干细胞研究进展盘点
PNAS：皮肤和骨髓中发现安全性高于iPS的新型干细胞
生物谷专访国家干细胞工程技术研究中心主任韩忠朝教授
干细胞分化的探秘路：从白血病">白血病到干细胞——生物谷专访李栋博士
2010细胞治疗研究进展与临床应用前沿研讨会
2010干细胞技术与应用讲座

Souped-Up Cellular Reprogramming

Changing a cell's fate by adding extra copies of a few genes has become routine in labs around the world. The technique, known as cellular reprogramming, allows scientists to turn back a cell's developmental clock, making adult cells behave like embryonic stem cells (see “Insights of the Decade,” p. 1612). The resulting induced pluripotent stem cells (iPSCs) are helping scientists to study a variety of diseases and may someday help to treat patients by supplying them with genetically matched replacement cells.

This year, scientists found a way to make reprogramming even easier using synthetic RNA molecules. The synthetic RNAs are designed to elude the cell's antiviral defenses, which usually attack foreign RNA. The technique is twice as fast and 100 times as efficient as standard techniques. And because the RNA quickly breaks down, the reprogrammed cells are genetically identical to the source cells, making them potentially safer for use in therapies.

Early evidence suggests that the RNA approach reprograms the cell more thoroughly than other methods do, yielding a closer match to embryonic stem cells. The method can also prompt cells to become nonembryonic cell types. By inserting synthetic RNA into a cell that codes for a key gene in muscle tissue, for example, the researchers could turn both fibroblasts and iPSCs into muscle cells.

外显子组测序/罕见疾病基因：通过只对某一基因组中的外显子（或者说是那个极小的实际编码蛋白质的基因组部分）进行测序，研究罕见遗传性疾病的研究人员能够发现造成至少12种疾病的特别的基因突变；这些遗传性疾病是由某个单独的有缺陷的基因引起的。

Brain：外显子测序揭示小脑共济失调的致病基因TGM6
Nature：外显子测序可用于疾病监测
Nature Genetics：外显子测序揭示罕见遗传疾病的致病原因
Science预测2010年科研热点

Homing In on Errant Genes

Scientists who study rare genetic disorders hit on a powerful strategy for finding the culprit DNA this year. Using cheap sequencing techniques and a shortcut—sequencing just the 1% of the genome that tells cells how to build proteins—they cracked several diseases that had eluded researchers until now.

The old way to track down the cause of Mendelian disorders, or diseases caused by a mutation in a single gene, was to study DNA inheritance patterns in families. That approach doesn't work when few relatives with the disease can be found or when a mutation isn't inherited but instead crops up spontaneously.

In late 2009, geneticists began sequencing just the exons, or protein-coding DNA, of patients with Mendelian disorders. (A few teams sequenced the patients' entire genome.) This “exome” sequencing yielded a long list of mutations that the scientists then winnowed, for example, by ignoring those that don't change protein structure or that many people carry. The end result: the faulty DNA underlying at least a dozen mystery diseases—including genes that lead to severe brain malformations, very low cholesterol levels, and facial deformities that look like a made-up Japanese Kabuki performer.

Finding the gene behind a rare disease can lead to better diagnosis and treatments and to new insights into human biology. Scientists hope to use exome sequencing to tick off the causes of more than half of some 7000 known or suspected Mendelian diseases that still don't have a genetic explanation.

量子模拟器：为了描绘在实验室所看见的情况，物理学家根据方程式推出了一些理论。这些方程式可能极其难以解出。但是在今年，研究人员通过量子模拟器发现了一条捷径——即在人造的晶体中，激光光点扮演着截留在光中的电子位置的离子和原子的角色。这些装置给在凝聚态物理学中的理论问题提供了快速的答案，它们可能最终会帮助人们解决诸如超导性等的谜团。

Quantum Simulators Pass First Key Test

Like a student who sneaks a calculator into a test, physicists have found a quick way to solve tough mathematical problems. This year, they showed that quantum simulators—typically, simulated crystals in which spots of laser light play the role of the crystal's ions and atoms trapped in the spots of light play the role of electrons—can quickly solve problems in condensed-matter physics.

Physicists usually invent theoretical models to explain experiments. They might approximate a magnetic crystal as a three-dimensional array of points with electrons on the points interacting through their magnetic fields. Theorists can jot down a mathematical function called a Hamiltonian encoding such an idealization. But “solving” a Hamiltonian to reveal how a system behaves—for example, under what conditions the electrons align to magnetize the crystal—can be daunting.

However, physicists can tailor a quantum simulator to a particular Hamiltonian and let the experiment solve the theoretical problem. Five groups reproduced the results for four previously solved Hamiltonians. Three even mapped “phase diagrams” akin to the one that shows the temperatures and pressures at which water becomes a gas, liquid, or solid.

Physicists hope quantum simulators will crack Hamiltonians that have not been solved—such as one for high-temperature superconductors. But first they had to show that the things could reproduce known results. Check.

分子动力学模拟：模拟蛋白质在折叠时的旋转一直是一种组合上的噩梦。如今，研究人员利用了世界上最强力的电脑之一的能力来跟踪在一个小的正在折叠的蛋白质中的原子运动，其能跟踪的时间要比过去任何一种方法都要长100倍。

D. E. Shaw et al., "Atomic-Level Characterization of the Structural Dynamics of Proteins," Science 330 , 341 (2010).

Molecular Dynamics Simulations

Sometimes brute force is the way to go, particularly when using computers to simulate the gyrations proteins make as they fold. Such simulations are a combinatorial nightmare. Each two neighboring amino acids in a protein chain can bind to one another at two different angles, each of which can have three conformations. So a simple protein with 100 amino acids can fold in 3198 different ways. Getting at the atomic detail is even scarier. Proteins sort through all these possibilities in milliseconds or less. Computers take far longer.

Protein-folding experts have long turned to supercomputers for help. But even these behemoths struggle to track the motions long enough to simulate the complete folding process. Two years ago, researchers in the United States unveiled a new supercomputer hardwired with 512 computer chips tailor-made to speed the calculations of the way neighboring atoms in a protein and the surrounding water interact. That enabled them to gain another burst in speed. As a result, the group reported this year that they've been able to track the motion of atoms in a small protein 100 times longer than previous efforts could do—long enough to see the protein wind its way through 15 cycles of folding and unfolding. Next up, the group is already turning to novel machines with 1024 and 2048 chips to improve simulations of larger proteins.

大鼠的回归：小鼠统治着实验室的动物世界，但研究人员为了诸多目的而更愿意用大鼠。人们更容易用大鼠来做实验，而大鼠在解剖上也与人类更加相似；但大鼠的重大缺陷是：用以制造“基因分离小鼠”——在这些动物中根据研究需要而将其某些特定的基因准确地关闭——的方法在大鼠中无效。然而，今年有一系列的研究承诺会给实验室带来大批的“基因分离大鼠”。

Nature：p53基因敲出的大鼠首次培育成功
Nature：基因敲除大鼠模型成功建立

Rats Redux

Today, most lab cages house mice, but the tenant of choice used to be rats. The reason: Rats are more like us. The human heart, for example, beats about 70 times a minute; a rat's heart, 300 times; a mouse's, 700. Electrical signal patterns in rat and human hearts are also similar. Rats, being more intelligent than mice, might also be better models of human neural diseases such as Alzheimer's and Parkinson's. And rats are bigger and easier to handle for lab work.

Then, in 1989, researchers learned to delete specific genes to make “knockout mice.” The technique they used, called homologous recombination of embryonic stem cells, didn't work in rats. So mice became the preferred experimental animal in various studies, from developmental biology to drug development.

That too may pass. In 2009, researchers adapted to rats a method, previously used in fruit flies and zebrafish, that uses enzymes called zinc finger nucleases to knock out genes. In August, another group announced a tweak that produced “knockout rats” by the same genetic trick used for knockout mice. Also this year, several groups reported advances in using transposons, DNA sequences that jump from one location to another within a genome, to generate rats with genetic mutations—animals useful for developmental biology and disease research. As a result of such techniques, knockout and genetically modified rats may soon displace their smaller cousins in lab cages around the world.

HIV预防：对预防HIV的两种不同且新颖的方法的试验报道了所取得的不容置疑的成功：一种含有抗HIV药物泰诺福韦（tenofovir）的阴道凝胶可使女性中HIV的感染减少39%，而一种口腔预先接触的预防法可令一组与男性发生性关系的男子和变性女子的HIV感染减少43.8%。

Science：可减少妇女HIV感染的阴道凝胶
NEJM：抗逆转录病毒药物对艾滋病有预防作用
The Lancet：鸡尾酒疗法有效降低HIV传播风险
Science：中和HIV的两种抗体
PLoS Pathog.：发现可抑制HIV传播的抑制剂
PNAS：HIV预治疗可能减少耐药株的数量
ACS Chem. Biol：预防HIV传播的新分子合成
Nature：HIV Tat复合物的晶体结构
Cell：Tetherin蛋白阻止HIV从细胞中释放机制
Nat. Biotech.：艾滋病基因治疗新进展
PLoS Comput Biol ：可快速判断HIV-1感染的电脑程序
Nature：HIV-1整合酶三维结构
JAMA：早期个性化抗逆转录病毒治疗HIV的重要性
Science：中和HIV的两种抗体
PLoS Pathog.：发现可抑制HIV传播的抑制剂
Nat. Biotech.：艾滋病基因治疗新进展
PNAS：HIV预治疗可能减少耐药株的数量
Nature：HIV Tat复合物的晶体结构
The Lancet：鸡尾酒疗法有效降低HIV传播风险
BMC Immunology ：接种天花疫苗或可预防艾滋病

HIV Prophylaxis

From the start of the AIDS epidemic through 2009, only five of 37 large-scale studies that attempted to prevent HIV yielded convincing, positive results. Then, this past July and November, two trials of different, novel HIV-prevention strategies unequivocally reported success. AIDS researchers all but danced with joy.

The first result stole the show at the jampacked XVIII International AIDS Conference held in Vienna, Austria. A vaginal gel that contains the anti-HIV drug tenofovir reduced HIV infections in high-risk women by 39% over a 30-month period. Nearly 900 South African women participated in the study, half receiving the microbicide and the others an inert gel. Among “high adherers,” women who used the microbicide exactly as instructed, its efficacy reached 54%.

Last month, the first-ever study of oral pre-exposure prophylaxis made headlines with results even more encouraging. The subjects, 2499 men and transgender women who have sex with men, were recruited from six countries. Half were asked to take Truvada, a combination of tenofovir and emtricitabine, each day. After an average of 1.2 years, the treated group had 43.8% fewer infections than the group that took a placebo. Again, better adherence equaled better efficacy: In a small substudy, efficacy increased to 92% in participants who had measurable levels of Truvada in their blood.

Neither approach is a magic bullet, AIDS researchers say. But in combination with other measures, they could usher in a new era of HIV prevention.