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<jats:p> Since the discovery of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> , dozens more breast cancer genes have come to light. But what risk they pose—and what to tell women who carry them—remain quandaries. </jats:p>

<jats:p>For more than 2 decades, Fran Visco, president of the National Breast Cancer Coalition, has been a force behind the second biggest U.S. breast cancer research program.</jats:p>

<jats:p> The existence of <jats:italic>BRCA1</jats:italic> was proven in 1990 by mapping predisposition to young-onset breast cancer in families to chromosome 17q21. Knowing that such a gene existed and approximately where it lay triggered efforts by public and private groups to clone and sequence it. The press baptized the competition “the race” and reported on it in detail for the next 4 years. <jats:italic>BRCA1</jats:italic> was positionally cloned in September 1994. Twenty years later, I reflect on “the race” and its consequences for breast cancer prevention and treatment. </jats:p>

<jats:p> The cloning of the breast cancer susceptibility genes <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> nearly two decades ago helped set in motion an avalanche of research exploring how genomic information can be optimally applied to identify and clinically care for individuals with a high risk of developing cancer. Genetic testing for mutations in <jats:italic>BRCA1</jats:italic> , <jats:italic>BRCA2</jats:italic> , and other breast cancer susceptibility genes has since proved to be a valuable tool for determining eligibility for enhanced screening and prevention strategies, as well as for identifying patients most likely to benefit from a targeted therapy. Here, we discuss the landscape of inherited mutations and sequence variants in <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> , the complexities of determining disease risk when the pathogenicity of sequence variants is uncertain, and current strategies for clinical management of women who carry <jats:italic>BRCA1/2</jats:italic> mutations. </jats:p>

<jats:p> Germline mutations in <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> predispose to common human malignancies, most notably tumors of the breast and ovaries. The proteins encoded by these genes have been implicated in a plethora of biochemical interactions and biological functions, confounding attempts to coherently explain how their inactivation promotes carcinogenesis. Here, I argue that tumor suppression by BRCA1 and BRCA2 originates from their fundamental role in controlling the assembly and activity of macromolecular complexes that monitor chromosome duplication, maintenance, and segregation across the cell cycle. A tumor-suppressive role for the BRCA proteins as “chromosome custodians” helps to explain the clinical features of cancer susceptibility after their inactivation, provides foundations for the rational therapy of BRCA-deficient cancers, and offers general insights into the mechanisms opposing early steps in human carcinogenesis. </jats:p>

<jats:title>Look After the Child</jats:title> <jats:p> Investing in children has been demonstrated to improve their lives, both during the school-age years and afterward, as assessed by outcomes such as employment and income; furthermore, these investments often help those in the most need. <jats:bold> Campbell <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1478" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248429">1478</jats:related-article> ) report that these investments can also lead to improved adult health. Results from a randomized and intensive intervention that involved 122 children in four cohorts recruited in the 1970s suggest that full-day child care for the first 5 years of life has produced adults in their 30s with better metabolic and cardiovascular health measures. </jats:p>

<jats:title>Mitoribosomes</jats:title> <jats:p> Mitochondria—found in all eukaryotic cells—have transferred most of their genes to the nuclear genome. The nuclear-localized mitochondrial genes are expressed and translated in the cytoplasm and the resulting mitochondrial proteins are imported into the mitochondria. Nevertheless, a few genes remain within mitochondria in the mitochondrial genome, and these genes are translated by mitochondrial ribosomes (mitoribosomes). <jats:bold> Amunts <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1485" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1249410">1485</jats:related-article> ; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1443" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1251652"> <jats:bold>Kühlbrandt</jats:bold> </jats:related-article> ) determined the structure of mitoribosomes from yeast using single-particle cryo–electron microscopy. The mitoribosome is highly diverged from the bacterial and eukaryotic ribosomes with, for example, a distinctive exit tunnel for the newly synthesized peptide, and a membrane facing protuberance that might help to anchor the mitoribosome to the mitochondrial membrane. </jats:p>

<jats:title>One-Sided Story from Disk</jats:title> <jats:p> In young analogs of the solar system, the ongoing erosion of comets and nascent planets produces dusty debris that is eventually expelled by the host star. Gas should also be released in this process when volatile ices sublimate, but it is detected less often. Using the Atacama Large Millimeter/Submillimeter Array, <jats:bold> Dent <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1490" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248726">1490</jats:related-article> , published online 6 March; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1440" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1251123">Brandeker</jats:related-article> </jats:bold> ) mapped a highly asymmetric disk of dust and carbon monoxide orbiting the planet-hosting star, β Pictoris. The distribution of gas and dust is consistent with two proposed scenarios: In one, an outward-migrating planet has resonantly trapped dust-yielding bodies in two clumps opposite the star. In another, the entire debris mass is the result of a single recent collision of Mars-sized bodies. </jats:p>

<jats:title>Beyond Brownian Motion</jats:title> <jats:p> On long time scales, the random Brownian motion of particles diffusing in a liquid is well described by theories developed by Einstein and others, but the instantaneous or short time scale behavior has been much harder to observe or analyze. <jats:bold> Kheifets <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1493" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248091">1493</jats:related-article> ) combined ultrasensitive position detection with sufficient data collection to probe the Brownian motion of microbeads in fluids on time scales that are shorter than the characteristic bead-fluid interaction time. </jats:p>

<jats:title>Controlling Quantum Plasmonics</jats:title> <jats:p> Electron tunneling across cavities could potentially induce a quantum mechanical plasmon mode that would be important in nano-electronics, catalysis, nonlinear optics, or single-molecule sensing, but has been expected to occur only at length scales beyond the reach of current state-of-the-art technology. Using a system of plasmonic dimers comprising silver nanocubes bridged by a molecular self-assembled monolayer, <jats:bold> Tan <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1496" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1248797">1496</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6178" page="1444" related-article-type="in-this-issue" vol="343" xlink:href="10.1126/science.1252245">Nordlander</jats:related-article> </jats:bold> ) observed quantum plasmonic tunneling between the resonators and were able to tune the frequency of this tunneling plasmon resonance via selection of the molecular tunnel junctions. Moreover, the effects were observed at length scales that are technologically accessible. </jats:p>