September 2004

Volume 18 Issue 17

The Scientist September 2004 Cover



Touching Every Person on the Planet

"There are no such things as applied sciences, only applications of science."- Louis Pasteur (1822–1895)It was said of the human genome project that it has the potential to influence the life of every person on the planet. That is a heroic aspiration, and one that can be achieved only through a business-science fusion unlike anything previously experienced.The process has already begun. Researchers are enthusiastically seeking opportunities to commercialize their work, with the full suppor


Stop Whispering About Peer Review

You switch on the evening news to hear a headline report of a small new study claiming unforeseen risks to health. The startling nature of the claims is, as so often happens, in inverse proportion to the study's sample size. The news program has already located a group of concerned parents and an apparently off-hand response from health officials. Over the ensuing days, add into the mix other interested parties, a 'maverick' scientist, vitriolic commentary drawing comparisons with thalidomide, a


Views on Plagiarism

While it may be true, as Shawn G. Clouthier writes, that "... most scientists agree on what constitutes scientific chicanery and malfeasance,"1 such agreement probably applies to the more egregious cases. Plagiarism, however, can manifest itself in a variety of subtler forms, and given the increasingly multidisciplinary and international nature of scientific research, these 'grayer' areas are likely to be a source of considerable disagreement.For example, the question of which forms of rewriting

On the Fat Tax

I'm sorry to hear that the discussion of a Fat Tax has taken such a tangential course.1 I have gone so far as to suggest a combined tax on fat and sugar, plus an increase in the taxes on tobacco and alcohol.But my purpose is not to change behavior. Nobody in their right mind would try to regulate behavior legislatively through taxation, although a high enough tax may dampen the enthusiasm for those with limited "discretionary income." Instead, the "sin taxes" are best levied for paying for the c


Where the wild things are (here)

Brad Fitzpatrick"We've got skinks. A lot of different skinks," notes Mike Osborn, an inspector with the US Fish and Wildlife Service (USFWS) in Los Angeles. It is a small shipment: about 1,000 gecko-like lizards from Egypt, packed in what appears to be squirmy pillowcases thumb-tacked to the sides of thin wooden crates. Osborn methodically opens the sacks to check whether they indeed hold skinks as it says on the manifest. They do: 25, 50, 75 per bag.Far from the familiar bustle of LAX's passeng

What lies beneath

"I'm all out of ideas," says hydrologist Mike Gooseff, still smiling despite his frustration.On a crisp, unusually warm and dry August afternoon on Alaska's North Slope, a few miles from the Toolik Lake Long-Term Ecological Research (LTER) field station, a two-meter metal rod is wedged in pristine streambed, irretrievable despite nearly an hour of yanking, pushing, prodding, and countless Rube-Goldberg-like brainstorms. Someone had forgotten to slip on a metal piece that would give a jack enough


Silencing Cancer

DELIVERY METHODS:© 2003, Elsevier ScienceSmall interfering RNAs (siRNAs) may be synthesized and then transfected into cells (A), or generated by the RNAase activity of Dicer (B) on short hairpin RNAs (shRNAs) transcribed in vivo (C). Transfection (D) and integration (E) of plasmid DNA containing a selectable marker and a promoter to drive shRNA expression are used to generate a stable cell line. Alternatively, DNA encoding shRNA may be introduced by viral-mediated transduction (D). siRNAs (

Hot Paper

Seeds of a Micro Revolution

MICRO TWISTS:Courtesy of Allison C. Mallory, Whitehead Institute for Biomedical ResearchA scanning electron micrograph of Arabidopsis shows the importance of microRNAs in development. A mutation in the CUC1 transcription factor rendering it impermeable to silencing by miR-164 results in flowers that have extra petals, missing sepals and altered floral organ position (at right).Among structural and regulatory RNAs, the newest kids on the block have sparked a flurry of breakthrough discoveries in


Fueling the Fires of RNA Interference

World RNAi Market 2010Contract service = outsourced research/target validation projects Total = Projected worldwide RNAi revenues for 2010, in US dollars Source: Frost & SullivanScientists hunger for breakthroughs in the lab, but it's the venture capitalists who continually scout the life sciences for the next great money-making bonanza. After a pivotal study in the May 2001 issue of Nature showed that RNA could effectively silence gene expression in mammalian cell lines, RNA interference (R


Now You're Signaling, With Gas

NO SIGNALING:© 2003 Annual ReviewsAll images redrawn from D. Boehning, S.H. Snyder, Ann Rev Neurosci, 26:105–31, 2003.Neuronal nitric oxide synthase (nNOS) is localized to NMDA receptors by the PDZ-domain adaptor protein PSD95. Calcium entry activates nNOS by a calcium/calmodulin-dependent mechanism. NO can diffuse to neighboring cells to activate soluble guanylyl cyclase or to nitrosylate cysteine residues on target proteins. Nitrosylation inhibits NMDA receptors providing a negative

Predicting Invasions from Satellite

TAMARISK ASSESSMENT:Courtesy of James ClossFour sites in Colorado and Utah where joint USGS-NASA teams are conducting studies of the invasive species, tamarisk.While aerospace engineers at NASA's Goddard Laboratories, northeast of Washington, DC, look down from the heavens, ecologists at a neighboring United States Geological Survey (USGS) have a closer view. Scientists from these disparate fields, ecology and aerospace, have begun collaborating in hopes of stemming a huge and ever-growing invas


The Language of Bacteria ... and Just About Everything Else

FIGURE 1:Courtesy of Kendra RumbaughEukaryotic and prokaryotic signaling molecules have similar functions. Mammalian steroid hormones bind to cognate nuclear hormone receptors; Pseudomonas aeruginosa autoinducer N-3-oxododecanoyl homoserine lactone acts as a ligand for the transcriptional activator LasR and is essential for cell-to-cell communication resulting in biofilm formation.Mammals possess sophisticated endocrine networks in which hormonal signals modulate hundreds of biological effects s


Better Structures Through Synergy

TRANSLATING THE RIBOSOME:© 2003 Nature Publishing GroupJoachim Frank and colleagues used cryo-electron microscopy to generate this image of the ribosome bound to release factor RF2 in the presence of a stop codon and a P-site tRNA (left). Then the team overlaid an atomic model of RF2, derived from X-ray data (right; colored orange, purple, red, and green to distinguish domains I, II, III, and IV, respectively). (Reprinted with permission, U.B.S. Rawat et al., Nature, 421:87–90, 2003.)

How It Works

Nuclear Magnetic Resonance Spectrometer

Nuclear magnetic resonance papers read like a veritable alphabet soup. There's NOESY, COSY, TOESY, and ROESY; HMQC, HMBC, HSQC, and DEPT. And let's not forget INEPT, INADEQUATE, EXSY, and SECSY.It's enough to make a biologist squirm. Yet fundamentally, these experiments all take advantage of a relatively simple physical phenomenon. Anybody who has ever turned a nail into a magnet by wrapping it with electrical wire knows magnetism and electricity are inextricably linked. NMR spectroscopists expl


Consider the Cycler

Earlier this summer scientists from New England Biolabs in Beverly, Mass., announced they had discovered a new way to copy DNA. Their method, called helicase-dependent amplification (HDA), reportedly mimics in vivo DNA replication better than PCR does.1 Moreover, HDA can be conducted at a single temperature, thus obviating the need for thermocycling. In the future, perhaps the limitations of PCR – that it is reagent intensive, requires expensive equipment, is difficult to reproduce, and ge


The Urge to Merge

CorbisWith pharma companies' pipelines relatively weak and many patents set to expire, 2004 is shaping up to be a strong year for mergers and acquisitions as firms look for a way to get quick access to products under development. In the first half of the year, acquisitions in the biotech-pharmaceutical industry nearly doubled to 315 from 177 in the last half of 2003, according to BioPharm Insight. Earlier this year Pfizer paid $1.42 billion (US) for Ann Arbor, Mich.-based Esperion Therapeutics,


Invitrogen Is Booming

Invitrogen HeadquartersCourtesy of InvitrogenWhen Invitrogen recruited General Electric Medical Systems executive Gregory Lucier to be its new CEO in May 2003, it looked like the biotechnology toolmaker was ready to take some lessons out of the big corporate textbook. Years in top positions at the old-economy giant had imbued Lucier with ideas such as financial discipline and operational efficiency, which don't always come naturally to companies pushing the cutting edge of science. Perhaps most


Improving Drug Delivery

Courtesy of Langer Research Lab, MITRobert Langer is a professor of chemical and biomedical engi neering at the Massachusetts Institute of Technology. He has written more than 800 articles, has more than 500 issued or pending patents worldwide, and has licensed his patents to 120 companies. In 2002 Langer was awarded the $500,000 Charles Draper prize, considered to be the Nobel Prize of engineering, and in 1999, Forbes Magazine named him one of the 25 most important people in biotechnology.Advan


The Focus on Quality Control

CorbisWhile it doesn't typically garner the lion's share of attention, quality control is just as important as other areas of science. If your R&D department comes up with the most promising compound of the century, without current Good Manufacturing Practices (cGMP) in place it may never get to patients. You need well-written procedures and properly maintained facilities and equipment, as well as quality assurance staff savvy enough to navigate the regulatory hurdles."Quality-control scient

FDA Update

FDA May Nix The "Not Approvable" Letter

Under a new proposal, the Food & Drug Administration may stop issuing "approvable" and "not approvable" letters to drug sponsors whose applications need to be revised or amended. Instead, companies would receive a "complete response" letter similar to those already used by the FDA for biologics. Using the same name for all the letters should help clear up some of the confusion that can be caused by the current system, according to John K. Jenkins, who heads the Office of New Drugs in the FDA

More Compounds Failing Phase I

More drugs in development are failing to make it to market, according to Acting FDA Commissioner Lester M. Crawford. Historically, 14% of drugs entering Phase I have won approval, Crawford said in a speech to the Banc of America Securities Healthcare Institutional Conference on July 7, but now only 8% reach the marketplace. One-half fail in Phase III, he added, compared to one in five in the past. This has pushed the cost of developing a drug from $1.1 billion in 1995 to $1.7 billion in 2002, he

New Cancer Office in the Works

Paul Richardson© 2004 ASCO/Todd BuchanonThe FDA is consolidating several divisions into a single Office of Oncology Drug Products (ODP) that will oversee drugs and certain therapeutic biologics targeted at cancer, as well as drugs and biologics for medical imaging. The office, which should be fully operational by April 2005, will be housed in the Center for Drug Evaluation and Research (CDER). The ODP will have three review divisions, but exactly how staff, products, and responsibilities wi

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