February 2009 Volume 27 Number 2, pp 101 - 208
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EDITORIAL
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The worst of times, the best of times p101
Big pharma should be more proactively investing in cash-hungry public biotech companies.
doi:10.1038/nbt0209-101
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NEWS
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Venture capital shifts strategies, startups suffer pp103 - 104
Peter Mitchell
doi:10.1038/nbt0209-103
http://links.ealert.nature.com/ctt?kn=72&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Merck joins the biotech game p104
Victor Bethencourt
doi:10.1038/nbt0209-104
http://links.ealert.nature.com/ctt?kn=114&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Biologic approvals in 2008 p105
doi:10.1038/nbt0209-105
http://links.ealert.nature.com/ctt?kn=143&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Osiris seals billion-dollar deal with Genzyme for cell therapy pp106 - 107
George S. Mack
doi:10.1038/nbt0209-106
http://links.ealert.nature.com/ctt?kn=13&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
GM poplars to grow next door p107
Hayley Birch
doi:10.1038/nbt0209-107a
http://links.ealert.nature.com/ctt?kn=40&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
FDA goes public-friendly p107
Emily Waltz
doi:10.1038/nbt0209-107b
http://links.ealert.nature.com/ctt?kn=52&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Avastin-Tarceva combination fails in lung cancer pp108 - 109
Dan Jones
doi:10.1038/nbt0209-108
http://links.ealert.nature.com/ctt?kn=134&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Stem cells caught in morality clause p109
Nayanah Siva
doi:10.1038/nbt0209-109a
http://links.ealert.nature.com/ctt?kn=48&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Land use stirs biofuels ruckus p109
Susan Kim
doi:10.1038/nbt0209-109b
http://links.ealert.nature.com/ctt?kn=25&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Cuba's first GM corn p110
Veronica Guerrero
doi:10.1038/nbt0209-110a
http://links.ealert.nature.com/ctt?kn=44&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
EU pushes advanced therapies p110
Susan Aldridge
doi:10.1038/nbt0209-110b
http://links.ealert.nature.com/ctt?kn=67&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
FDA holds court on post hoc data linking KRAS status to drug response pp110 - 112
George S. Mack
doi:10.1038/nbt0209-110c
http://links.ealert.nature.com/ctt?kn=26&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
DATA PAGE
2008 - down, but not out p113
Walter Yang
doi:10.1038/nbt0209-113
http://links.ealert.nature.com/ctt?kn=120&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
NEWS FEATURE
Glial cells on the radar pp114 - 116
Long thought of as passive bystanders, glial cells are coming under increasing scrutiny as mediators of inflammatory disease in the nervous system. Now, some drug makers are hoping they can be targeted pharmacologically. Cormac Sheridan reports.
Cormac Sheridan
doi:10.1038/nbt0209-114
http://links.ealert.nature.com/ctt?kn=108&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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BIOENTREPRENEUR
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BUILDING A BUSINESS
Avoiding the obvious
Obviousness is one of the most common reasons for examiners rejecting patent applications. What can you do to limit the chances of such a setback?
Sherry L Murphy and Kenneth D Sibley
doi:10.1038/bioe.2008.12
http://links.ealert.nature.com/ctt?kn=88&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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OPINION AND COMMENT
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CORRESPONDENCE
The next generation p120
Fern Wickson
doi:10.1038/nbt0209-120a
http://links.ealert.nature.com/ctt?kn=124&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
The next generation pp120 - 121
Justin Chakma
doi:10.1038/nbt0209-120b
http://links.ealert.nature.com/ctt?kn=104&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Gunvalson and PTC Therapeutics' community outreach pp121 - 122
Stuart W Peltz
doi:10.1038/nbt0209-121
http://links.ealert.nature.com/ctt?kn=121&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
DNA sequence patents are not in the grave yet p122
Robert Cook-Deegan and Arti K Rai
doi:10.1038/nbt0209-122
http://links.ealert.nature.com/ctt?kn=149&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
COMMENTARY
A lifeline for the biotech sector pp123 - 124
With many small biotech companies teetering at the edge of a financial precipice, the US government should act swiftly to enact tax benefits allowing a refund of net operating losses.
Mark Kessel
doi:10.1038/nbt0209-123
http://links.ealert.nature.com/ctt?kn=47&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Charting a course through a perfect storm pp125 - 127
A venture capitalist gives his perspective on the outlook for life sciences ventures amid the perfect storm of the current economic downturn.
Arthur Klausner
doi:10.1038/nbt0209-125
http://links.ealert.nature.com/ctt?kn=5&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
BOOK REVIEW
The bioentrepreneur's road map p128
Michael R Bielski reviews Commercializing Successful Biomedical Technologies: Basic Principles of the Development of Drugs, Diagnostics and Devices by Shreefal S Mehta
doi:10.1038/nbt0209-128
http://links.ealert.nature.com/ctt?kn=65&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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FEATURES
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The cancer vaccine roller coaster pp129 - 139
The cancer vaccine field is littered with promising products that failed to show clinical efficacy. Could it finally be on the verge of a first US approval?
Bruce Goldman and Laura DeFrancesco
doi:10.1038/nbt0209-129
http://links.ealert.nature.com/ctt?kn=95&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
PATENTS
Proprietary science, open science and the role of patent disclosure: the case of zinc-finger proteins pp140 - 144
A closer look at the large patent estate now covering both the engineering and use of zinc-finger proteins.
Subhashini Chandrasekharan, Sapna Kumar, Cory M Valley and Arti Rai
doi:10.1038/nbt0209-140
http://links.ealert.nature.com/ctt?kn=75&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Recent patent applications in gene expression p145
doi:10.1038/nbt0209-145
http://links.ealert.nature.com/ctt?kn=39&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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NEWS AND VIEWS
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Year of the ox pp146 - 147
High levels of human polyclonal antibodies have been produced in a transgenic large animal.
Yann Echelard
doi:10.1038/nbt0209-146
http://links.ealert.nature.com/ctt?kn=96&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
One photon up, one photon down pp147 - 148
A microscopy technique based on stimulated Raman scattering achieves label-free imaging with very high sensitivity.
Enrico Gratton and Michelle Digman
doi:10.1038/nbt0209-147
http://links.ealert.nature.com/ctt?kn=77&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Knocking sense into regulatory pathways pp149 - 150
Simultaneous targeted perturbations illuminate the structure and function of regulatory networks.
Guri Giaever and Corey Nislow
doi:10.1038/nbt0209-149
http://links.ealert.nature.com/ctt?kn=82&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Sequencing in real time pp150 - 151
DNA synthesis by single polymerase molecules has been visualized at the speed of catalysis, heralding a new sequencing technology of unparalleled throughput.
Michael L Metzker
doi:10.1038/nbt0209-150
http://links.ealert.nature.com/ctt?kn=74&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Research highlights p152
doi:10.1038/nbt0209-152
http://links.ealert.nature.com/ctt?kn=34&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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COMPUTATIONAL BIOLOGY
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PRIMER
Understanding genome browsing pp153 - 155
How can genome browsers help researchers to infer biological knowledge from data that might be misleading?
Melissa S Cline and W James Kent
doi:10.1038/nbt0209-153
http://links.ealert.nature.com/ctt?kn=43&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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RESEARCH
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REVIEW
Protein promiscuity and its implications for biotechnology pp157 - 167
Irene Nobeli, Angelo D Favia and Janet M Thornton
doi:10.1038/nbt1519
Abstract: http://links.ealert.nature.com/ctt?kn=3&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=17&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
BRIEF COMMUNICATIONS
Transgenic mice with defined combinations of drug-inducible reprogramming factors pp169 - 171
The generation of induced pluripotent stem cells might be improved by replacing the reprogramming transgenes with small molecules. To provide cells suitable for small-molecule screening, Markoulaki et al. segregate the transgenes Oct4, Sox2, Klf4 and c-Myc through breeding, creating mice carrying all possible combinations of the four factors.
Styliani Markoulaki et al.
doi:10.1038/nbt.1520
Abstract: http://links.ealert.nature.com/ctt?kn=87&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=154&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
ARTICLES
Antigen-specific human polyclonal antibodies from hyperimmunized cattle pp173 - 181
A reliable supply of antigen-specific human antibodies could be useful for treating many diseases. Kuroiwa et al. use multiple rounds of genetic modification and cloning to generate a calf carrying human immunoglobulin genes and lacking bovine immunoglobulin genes, and show that the hyperimmunized animal produces >2 g/l of antigen-specific human polyclonal antibodies.
Yoshimi Kuroiwa et al.
doi:10.1038/nbt.1521
Abstract: http://links.ealert.nature.com/ctt?kn=54&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=30&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Solution hybrid selection with ultra-long oligonucleotides for massively parallel targeted sequencing pp182 - 189
Gnirke et al. present a bead-based method for capturing sequences of interest in the human genome for massively parallel sequencing. Using long, biotinylated RNA probes to pull down PCR-amplified DNA fragments, they demonstrate sequencing of 2.5 Mbs of exons in 1,900 genes.
Andreas Gnirke et al.
doi:10.1038/nbt.1523
Abstract: http://links.ealert.nature.com/ctt?kn=141&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=115&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Prediction of high-responding peptides for targeted protein assays by mass spectrometry pp190 - 198
Development of sensitive mass spectrometry-based assays for complex biofluids depends on the ability to identify signature peptides that produce the strongest signals. Fusaro et al. use protein physicochemical properties to predict high-responding peptides in data obtained from complex samples such as plasma.
Vincent A Fusaro, D R Mani, Jill P Mesirov and Steven A Carr
doi:10.1038/nbt.1524
Abstract: http://links.ealert.nature.com/ctt?kn=86&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=45&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
LETTER
Dynamic modularity in protein interaction networks predicts breast cancer outcome pp199 - 204
Altered gene expression in tumors has been explored as a prognostic indicator of cancer outcome and treatment efficacy. Taylor et al. extend this approach by analyzing the coordinated expression of 'hub' proteins and their interacting partners as a means of predicting breast cancer prognosis.
Ian W Taylor et al.
doi:10.1038/nbt.1522
Abstract: http://links.ealert.nature.com/ctt?kn=71&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Article: http://links.ealert.nature.com/ctt?kn=123&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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CORRIGENDUM
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Corrigendum: What's fueling the biotech engine - 2007 p205
Saurabh Aggarwal
doi:10.1038/nbt0209-205a
http://links.ealert.nature.com/ctt?kn=85&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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ERRATA
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Erratum: What's fueling the biotech engine - 2007 p205
Saurabh Aggarwal
doi:10.1038/nbt0209-205b
http://links.ealert.nature.com/ctt?kn=28&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Erratum: Asymmetric RNA duplexes mediate RNA interference in mammalian cells p205
Xiangao Sun, Harry A Rogoff and Chiang J Li
doi:10.1038/nbt0209-205c
http://links.ealert.nature.com/ctt?kn=57&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Erratum: Profile: Alan Alda p205
George S Mack
doi:10.1038/nbt0209-205d
http://links.ealert.nature.com/ctt?kn=135&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Erratum: Biotech sector ponders potential 'bloodbath' p205
Peter Mitchell and Brady Huggett
doi:10.1038/nbt0209-205e
http://links.ealert.nature.com/ctt?kn=133&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
Erratum: Doubts surround link between Bt cotton failure and farmer suicide p205
Cormac Sheridan
doi:10.1038/nbt0209-205f
http://links.ealert.nature.com/ctt?kn=127&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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NATUREJOBS
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CAREERS AND RECRUITMENT
Fear factor pp206 - 207
Job prospects are looking gloomy as the economic downturn runs its course, but there are bright spots for some.
Genevive Bjorn
doi:10.1038/nbt0209-206
http://links.ealert.nature.com/ctt?kn=63&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
PEOPLE
People p208
doi:10.1038/nbt0209-208
http://links.ealert.nature.com/ctt?kn=91&m=31308050&r=MTc3MTg2NzE2NgS2&b=2&j=NDU2Njc5MTcS1&mt=1&rt=0
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