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The Bibliome

Lists always leave something out. But we decided to give it a go anyway. We culled compilations of noteworthy publications and harassed brilliant people. Finally, after difficulty, disputation, and trepidation, we agreed on the list below. These papers highlight areas that will grow in importance over the next few years.


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SARS: Vulnerability Unmasked

CITATION Ksiazek, T.G. et al. (May 15, 2003) A novel coronavirus associated with severe acute respiratory syndrome. New England Journal of Medicine 348:1953–66.

SUMMARY Human vulnerability to viruses both natural and engineered became clear and pressing during the SARS epidemic. Researchers quickly pinned the syndrome on a coronavirus. Collaboration, coöperation, and infection-control tactics have kept the number of deaths below 1,000. The animal source and extent of recurrence are still unknown, but with any luck, we’re more prepared for the next outbreak.

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FIELD Public health

IMPACT Global efforts to control outbreaks will be more coördinated.

DIAGNOSTICS Coming soon: more and better tests for infectious diseases.

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Genetic Modification, Friend and Foe

CITATION Squire, G.R. et al. (November 29, 2003) On the rationale and interpretation of the Farm Scale Evaluations of genetically modified herbicide-tolerant crops. Philosophical Transactions of the Royal Society of London Series B, Biological Sciences. 358:1779–99.

SUMMARY The first large-scale study of the environmental impact of three genetically modified crops bore mixed, but not necessarily inconclusive, results. Depending on herbicide use, GM crops may support more, or fewer, invertebrate and weed species. This only goes to show that genetic modification as a whole cannot be condemned or lauded; whether benefits outweigh risks must be decided case by case.

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FIELD Agbio

IMPACT Needed: a nuanced debate. Dreaded: blanket policies.

INSIGHT Health and environmental risks depend more on how crops are grown than modified.

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The Stem Cell Fusion Illusion

CITATION Alvarez-Dolado, M. et al. (October 30, 2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–73.

SUMMARY Transplanted bone marrow cells probably form new kinds of tissues not by transforming into specialized cells but by fusing with them. This overturns the rationale for adult stem cells as a replacement for the embryonic variety, and suggests that adult stem cells’ ability to generate new cell types is limited.

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FIELD Stem cell therapies

IMPACT Bans on embryonic stem cell research stave off new cures.

THERAPIES Cell fusion could preserve damaged liver, brain, and other tissues.

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A Single Receptor Makes Life-Death Decisions

CITATION Micheau, O., J. Tschopp (July 25, 2003) Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 114:181–90.

SUMMARY Because controlled cell death is required for healthy living, apoptosis is controlled by many mechanisms. One of the most powerful, common, and confusing of these involves TNF receptor I, which causes both cells’ death and their continued vigor. An understanding of the process offers ways to manipulate it, potentially affecting disorders like cardiovascular and neurological diseases and cancer.

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FIELD Cancer, cell biology, degenerative diseases

IMPACT One signal rouses proteins in two pathways: one causes cell death; one stops it.

THERAPIES Controlling cell death and survival are key to treating a myriad of diseases.

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’Omics Prognosis

CITATION Yanagisawa, K. et al. (August 9, 2003) Proteomic patterns of tumour subsets in non-small-cell lung cancer. The Lancet 362:433–9.

SUMMARY Both gene expression profiling and its more complicated cousin, protein profiling, could help physicians choose between aggressive therapy and palliative care. For some cancers, profiling distinguishes among patients with different subtypes of the disease and between short and long survival times. Trials assessing the techniques’ reliability will mushroom next year.

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FIELD Molecular pathology

IMPACT Technique shows most revealing genetic differences.

TOOLS More meaningful markers make finding disease-linked genes easier.

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Protein Networking for a Whole Genome

CITATION Giot, L. et al. (November 6, 2003) A protein interaction map of Drosophila melanogaster. Science, published online before print.

SUMMARY Genes provide an idea of which proteins exist but not what they do. Knowing which proteins work together can lead to that understanding and enhance the ability to treat disease. A map of these interactions in the fruit fly confirmed known interactions, and extended and uncovered new ones. Human maps are under way, but their contents are proprietary.

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FIELD Systems biology

IMPACT Map helps pick best proteins and pathways for drug discovery.

INSIGHT Unexpected protein interactions uncover basic cell biology.

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Dying Cells Tell Tales

CITATION Shi, Y., J.E. Evans, K.L. Rock (October 2, 2003) Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425:516–21.

SUMMARY Cells dying from damage or infection alert the immune system to trouble. The nature of the signal has been elusive. Recent work shows that it comes from the damaged cells themselves, in the form of a simple molecule produced when DNA degrades. This discovery points to ways to tune the immune response.

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FIELD Immunology and vaccines

IMPACT Crucial component of body’s 911 system found.

THERAPIES Danger signal could boost vaccines and inform autoimmune treatments.

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Hunting Genes for Mental Illness and More

CITATION Segurado, R. et al. (July 2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: bipolar disorder. American Journal of Human Genetics 73:49–62.

SUMMARY When various researchers go hunting for genes that contribute to complex diseases, they rarely find the same genes. Published studies can separate, to some degree, true genetic culprits from potential artifacts. More of these meta-studies, about conditions from atherosclerosis to obesity, will pour forth in the coming years.

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FIELD Mental health, complex diseases

IMPACT Genetic markers can permit earlier disease detection and better control.

THERAPIES Pinning diseases on certain genes reveals new drug targets.

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Gene Silencing Still Making Noise

CITATION Rubinson, D.A. et al. (March 2003) A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNAi. Nature Genetics 33:401–6.

SUMMARY Since its discovery just a few years ago, silencing genes with short interfering RNA has become a standard procedure for figuring out how drugs might work. Many companies think small interfering RNA can be used as a drug itself. The problem, both for screening mammalian genes and developing drugs, has been getting the RNA molecules inside cells. Viruses, an old problem, may be the answer.

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FIELD Drug discovery and delivery

IMPACT Finally, a broadly effective way to probe mammalian gene functions.

THERAPIES Technique offers new starting point to stop bad genes.

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SOURCES: Faculty of 1000, BioMed Central; Science Watch; Thomson ISI; Acumen

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