Table of contents



America's got talent—can it keep it? p181


To remain competitive in biotech, policymakers should pay more attention to retaining skilled foreign workers than to fixating on illegal immigration.

H1N1dsight is a wonderful thing p182


Criticisms of the response of governments and of the pharmaceutical industry to the threat of the H1N1 epidemic are wide of the mark.



Ark's gene therapy stumbles at the finish line pp183 - 184

Peter Mitchell


Monsanto's alfalfa reaches Supreme Court p184

Boonsri Dickinson


GSK/Sirtris compounds dogged by assay artifacts pp185 - 186

Charlie Schmidt


US biodefense contracts continue to lure biotechs pp187 - 188

Catherine Shaffer


Ride 'n Drive on government waste p188


Melanoma vaccine for dogs p189

Suzanne Elvidge


Biotechs go virtual p189

Susan Aldridge


Chinese institute makes bold sequencing play pp189 - 191

John Fox & Jim Kling


RNAi delivery shop p191

Nazlie Latefi


Brazil boosts bioscience p191

Ricardo Bonalume Neto


Patent income tax slashed p192

Asher Mullard


Abbott hit with record fine p192

Michael Francisco


Resuscitated deCODE refocuses on diagnostics p192

Mark Ratner


News Features

One year in—Obama's biotech scorecard pp193 - 196

Jeffrey L Fox


As healthcare reform falters, the biotech industry awaits the fate of biosimilars and tax credits. Jeff Fox reports.

The lengthening handshake pp197 - 199

Randy Osborne


Although mergers and acquisitions (M&As) failed to hit the heights some analysts had predicted in 2009, a new type of tiered transaction rose to prominence—the structured deal. Randy Osborne reports.



Building a business

Seeking the biotech eBay pp200 - 202

Nuala Moran



Opinion and Comment


Oversulfated chondroitin sulfate is not the sole contaminant in heparin pp203 - 207

Jing Pan, Yi Qian, Xiaodong Zhou, Andrew Pazandak, Sarah B Frazier, Peter Weiser, Hong Lu & Lijuan Zhang


Why FDA recruitment of 'critics' is a problem p212

Henry I Miller


Genetic exceptionalism pp212 - 213

William Bains




Lost in migration pp214 - 229

George S Mack & Andrew Marshall


Combinations of cytostatic treatments and chemotherapies currently in clinical practice offer limited hope for patients whose cancers have spread. But increasing understanding of the processes underlying metastasis may one day provide other therapeutic options.


Patenting biotech beyond the central dogma pp230 - 233

George Wu


Biotech inventors and patent practitioners alike need to be aware of new interpretations of what is considered patentable, and draft claims that extend beyond biological principles.

Recent patent applications in DNA diagnostics p234



News and Views

Genetic therapy for spinal muscular atrophy pp235 - 237

Alex MacKenzie


A severe inherited neuromuscular disease is corrected in mice by intravenous gene delivery.

See also: Research by Foust et al.

Targeting leukemia stem cells pp237 - 238

Hanna K A Mikkola, Caius G Radu & Owen N Witte


Acute myeloid leukemia stem cells can be made susceptible to chemotherapy by inducing them to divide.

See also: Research by Saito et al.

Cellular targets for influenza drugs pp239 - 240

Ji-Young Min & Kanta Subbarao


High-throughput RNAi screens in human cells suggest new approaches to curb influenza virus infection.

Navigating genomic maps of cancer cells pp241 - 242

Marcel P van der Brug & Claes Wahlestedt


What can we learn from the first genome sequences obtained from cancerous cells?

Grass genomics on the wild side p242

Craig Mak



Research Highlights

Research highlights p243

Markus Elsner, Laura DeFrancesco & Craig Mak



Computational Biology


What is flux balance analysis? pp245 - 248

Jeffrey D Orth, Ines Thiele & Bernhard Ø Palsson


Flux balance analysis is a mathematical approach for analyzing the flow of metabolites through a metabolic network. This primer covers the theoretical basis of the approach, several practical examples and a software toolbox for performing the calculations.




Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis pp249 - 255

Vishal M Gohil, Sunil A Sheth, Roland Nilsson, Andrew P Wojtovich, Jeong Hyun Lee, Fabiana Perocchi, William Chen, Clary B Clish, Cenk Ayata, Paul S Brookes & Vamsi K Mootha


Many diseases are characterized by shifts in cellular energy metabolism. Gohil et al. use a quantitative, nutrient-sensitized screen to identify drugs that affect the relative rates of glycolysis and mitochondrial respiration, and demonstrate the protective capacity of an approved antiemetic in models of cardiac and cerebral ischemia.

Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein pp256 - 263

Peter O Bauer, Anand Goswami, Hon Kit Wong, Misako Okuno, Masaru Kurosawa, Mizuki Yamada, Haruko Miyazaki, Gen Matsumoto, Yoshihiro Kino, Yoshitaka Nagai & Nobuyuki Nukina


Decreasing levels of mutant, but not normal, huntingtin (HTT) protein remains a major obstacle to treating Huntington's disease (HD). Bauer et al. show that a fusion of polyglutamine-and HSC70–binding motifs specifically targets mutant HTT for degradation by chaperone-mediated autophagy and ameliorates the phenotype of a mouse model of HD.

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine pp264 - 270

Mikhail G Shapiro, Gil G Westmeyer, Philip A Romero, Jerzy O Szablowski, Benedict Küster, Ameer Shah, Christopher R Otey, Robert Langer, Frances H Arnold & Alan Jasanoff


Magnetic resonance imaging of hemoglobin in the brain can detect blood flow associated with neural activity, but direct imaging of neurotransmitters would provide a more sensitive measure of neural signal processing. Shapiro et al. use directed evolution to generate a protein probe that enables magnetic resonance imaging of the neurotransmitter dopamine.


Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN pp271 - 274

Kevin D Foust, Xueyong Wang, Vicki L McGovern, Lyndsey Braun, Adam K Bevan, Amanda M Haidet, Thanh T Le, Pablo R Morales, Mark M Rich, Arthur H M Burghes & Brian K Kaspar


Spinal muscular atrophy is an autosomal recessive disease of motor neurons caused by lack of the SMN gene. Foust et al. achieve long-term correction of the disease phenotype in a mouse model by intravenous delivery of SMN using the viral vector scAAV9.

See also: News and Views by MacKenzie

Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML pp275 - 280

Yoriko Saito, Naoyuki Uchida, Satoshi Tanaka, Nahoko Suzuki, Mariko Tomizawa-Murasawa, Akiko Sone, Yuho Najima, Shinsuke Takagi, Yuki Aoki, Atsushi Wake, Shuichi Taniguchi, Leonard D Shultz & Fumihiko Ishikawa


In acute myeloid leukemia, a sub-population of quiescent cancer cells, called leukemia stem cells, is thought to be responsible for chemotherapy resistance and eventual recurrence of the disease. Saito et al. show that treatment with granulocyte colony-stimulating factor can overcome resistance to standard therapy by inducing cell cycle entry of the leukemia stem cells.

See also: News and Views by Mikkola et al.

Isotopic labeling of terminal amines in complex samples identifies protein N-termini and protease cleavage products pp281 - 288

Oded Kleifeld, Alain Doucet, Ulrich auf dem Keller, Anna Prudova, Oliver Schilling, Rajesh K Kainthan, Amanda E Starr, Leonard J Foster, Jayachandran N Kizhakkedathu & Christopher M Overall


Many proteases are important drug targets, but identification of their substrates remains challenging. By using polymers to selectively isolate N-terminal peptides generated by proteolysis of complex samples, Kleifeld et al. identify substrates of clinically relevant proteases with broad specificity.


Careers and Recruitment

The importance of foreign-born talent for US innovation pp289 - 291

Yeonji No & John P Walsh


A survey suggests that foreign-born scientists and engineers play a major role in scientific and innovation output in the United States.


People p292