June 2004

Volume 18 Issue 11

The Scientist June 2004 Cover

Departments

Editorial

Will Life Sciences Follow Suit?

Arash of globalization is transferring upscale jobs offshore. This is the politically charged business practice of sending high-paying jobs out of the United States and Western Europe to Eastern Europe and developing countries, where salaries are considerably lower.For us, there are two questions: Will life sciences research, industrial or academic, follow this offshore trend? And if so, who will be the winners and the losers?The life sciences have so far been pretty deaf to the siren song of ou

Opinion

The Myth of Delayed Recognition

Brad FitzpatrickMost scientists can name an example of an important discovery that had little initial impact on contemporary research. Mendel's work is a classic example.12 The phenomenon of delayed recognition is sometimes invoked in disputes about the validity of citation analysis in evaluating scientists. However, as bibliometricians know, actual examples of delayed recognition are rare.To identify such papers and to shed some light on their role in scientific communication, we analyzed progr

Letter

Some Haplotype History

I enjoyed the article on the controversy concerning the utility of haplotypes in human disease understanding.1 My assessment is more in line with Ken Kidd's than with the fervent advocates of the HapMap.My interest in this area dates from the 1970s and culminated in 1989–1990 with two patents concerning the utility of haplotypes marked by noncoding sequence variant markers exhibiting linkage disequilibrium http://www.SimonsJunkDNA.com. Those articles indicate that HLA scientists have under

Science and Media Culture Clash

I read your editorial with interest,1 since most of my career as a journalist has been spent writing about scientific and technical topics. A few observations:1. Most scientists are elitist. They seem to feel that no one bereft of a PhD in their fields can possibly understand what they will say, so therefore they feel no obligation to simplify their presentations.2. Reporters want the who, what, where, when, why, and how. Note the order here. The why and how, which are the meat of the story for

5-Prime

The Basics of Biotechnology

What does 'bio-technology' mean?The term comes from Fernando Silva da Bioteqnolojo, a 16th century venture capitalist who sold shares in the Fountain of Youth to Madrid laborers. Not buying it? Okay, biotechnology is a term that first appeared in the 1970s to describe the use of biological techniques for creating commercially useful products, mostly protein-based pharmaceuticals. One of the first successful biotech companies, Genentech, found a way to produce insulin using vats filled with anaer

Frontlines

Blocking Bitterness

Drowning bitter-tasting pharmaceuticals in sweeteners or dispersing them into liposomes, microcapsules, or gums are standard ways to get people to swallow medications such as antibiotics, cold remedies, and ulcer medications. Cranbury, NJ-based Linguagen is developing a new approach using the signal transduction pathways that underlie taste: The company is screening libraries of small, natural molecules to be used as additives that would block the binding of bitter-tasting compounds before the b

Snapshot

vCJD and CJD by the Numbers

As of Dec. 1, 2003, 153 cases of variant Creutzfeldt-Jakob disease (vCJD) were reported: 143 in the United Kingdom, 6 in France, and 1 each in Italy, Canada, Ireland, and the United States. Nearly all of the affected people had been in the UK between 1980 and 1996, during a large bovine spongiform encephalopathy outbreak.Between 1997 and 2003, 731 cases of CJD – sporadic, familial and iatrogenic – were reported in the United States. The rate of deaths due to this type of CJD has rema

Foundations

Finding the Achilles' Heel of AIDS

Courtesy of the Michael H. Malim LabFor about 10 years, our laboratory had been trying to elucidate why the HIV Vif protein is essential for virus replication. Since 1998, we had suspected that Vif 's role was to inhibit a cellular protein that naturally blocks infection. This scintillation counter printout from December 2001 shows that varying amounts of a candidate inhibitor gene we had identified, called APOBEC3G/CEM15, profoundly suppress infection (measured as radioactivity in the CPM colum

Frontlines

Humor and Handedness

When Seana Coulson, assistant professor of cognitive science, and her graduate student, Christopher Lovett, looked for a high-level language task to study brain responses in right- and left-handers, the investigators turned to humor. The University of California, San Diego, researchers recorded brainwaves in 16 righties and 16 lefties while they read jokes, such as "I still miss my ex-wife, but I am improving my aim"; or nonsequiturs, such as "I still miss my ex-wife, but I am improving my ego."

First Person

Peter Wagner

Tell us about your scientific evolution as an adultCourtesy of Peter WagnerI left Germany in 1989 for Switzerland. I was always interested in interdisciplinary work, and I enjoy going to places to find smart people. I studied biochemistry and chemistry in Switzerland and Germany. I received a Humboldt Fellowship from Germany to study at Stanford. I arrived in the US in 1995.What did you do at Stanford?When I left Switzerland, I combined three fields: protein engineering with materials science an

Feature

Clearing Hurdles: Prions Know How to Do It

INDUCING DISTINCT YEAST PRION STRAINS:©2004 Nature Publishing Group[PSI+] using amyloid fibers derived from a recombinant Sup35p fragment [Sup-NM] at 4°C, 23°C and 37°C. White and pink and/or sectored colonies are strong and weak [PSI+] variants, respectively. (Nature, 428:323–7, 2004)In the relative quiet following the outbreak of bovine spongiform encephalopathy in the United Kingdom, BSE returned to the headlines recently with a sole case found in the United States a

Research

Vaccines on Trial: HIV

This past May, non-profit organizations and hospitals promoted AIDS Vaccine Awareness Day, in some places displaying the traditional AIDS awareness symbol, a red ribbon, upside down – forming a V for vaccine. But it is hardly a V for victory. Even though 19 countries are testing upwards of 30 vaccine candidates, only 2 have advanced to clinical Phase III efficacy trials, according to the International AIDS Vaccine Initiative (IAVI). Candidates in Phase I/II, II, and III include viral vecto

Are HIV Vaccines Fighting Fire with Gasoline?

An effective HIV vaccine has yet to be created, and maybe one never will. Scientists working on protective vaccines have mountains of problems with the virus' slippery nature, but perhaps most unnerving is that a vaccine-primed immune system might be more susceptible to infection. Boosting the HIV-specific helper cells may be giving the virus more factories in which to reproduce.T helper (Th) cells have a "dual role as target cells for infection, as well as being important mediators of the host

Hot Paper

Vaccine Trials Sobered by Breakthrough Mutation

PROFILING AN ESCAPEE:In A, cellular peptide binding assays of the wild-type p11C peptide and the mutant peptide (p11C*) for the MHC class i molecule Mamu-a*01 show reduced recognition for the mutant. The p11B peptide serves as an irrelevant control. In B, functional interferon g assays done on cell lines from monkeys 893, 833, and 798 show reduced response to peptide p11C in monkey 798 52 weeks after challenge.Clinical research by nature begets clichés: ups and downs, one step forward, one

Research

Humanizing Protein Splicing

IT SLICES, IT DICES, IT EVEN SPLICES:©2004 Nature Publishing Group H.-G. Rammensee, Nature, 427:203–4, Jan. 15, 2004.Initial models of protein splicing (as shown at left) had protein cleavage and ligation occurring through unidentified processes, with further truncation occurring in the proteasome. Further evidence suggests that the proteasome actually mediates both hydrolysis and reformation of amide bonds (as shown at right) and that remaining N-terminal amino acids are removed in t

Vision

Behold the Talking Chimp

SMALL HINTS, LARGE CHANGES:Courtesy of Rick Effland; Design, Erica P. JohnsonAlthough the genetic differences are small, as illustrated in the above stretch of FOXP2, and the neural differences still largely unknown, there is a world of difference between the mind of a chimp and the mind of a human.From our common ancestor with chimpanzees, it took only six million years, give or take, to develop the ability to speak. And, as we now know, the vast majority of our genetic material has been inheri

Briefs

A Toll-like Take on Cancer Vaccines

Courtesy Jean-Robert Brisson NRC Inst. Biological SciencesCD8+ T-cell tolerance of tumors can block an aggressive immune response against cancer and may diminish the efficacy of therapeutic vaccines. But Yiping Yang, a Duke University immunologist, says he and his colleagues have found a way to overcome T-cell tolerance using the immune system's innate response to pathogens. Membrane-bound Toll-like receptors (TLRs) detect repetitive epitopes commonly found in pathogens. Activating these recepto

Transgenic Mosquitoes: Fit to Fly?

Courtesy of Cristina K. MoreiraAt least two years ago, scientists began creating genetically engineered mosquitoes with reduced capacity to transmit malarial parasites. But recent studies offer mixed messages as to whether bio-engineered skeeters can compete in the wild.In a laboratory study with Anopheles stephensi, Case Western Reserve University's Marcelo Jacobs-Lorena and colleagues showed that a transgene encoding the protein SM1, which interrupts parasite development, did not affect mosqui

Interdisciplinary Research

These papers were selected from multiple disciplines from the Faculty of 1000, a Web-based literature awareness tool http://www.facultyof1000.com.G. Hutvágner et al., "Sequence-specific inhibition of small RNA function," PLoS Biol, 2:E98, April, 2004.Hutvágner et al. have shown that 2'-O-methyl oligonucleotides stoichiometrically and irreversibly inhibit the activity of [microRNAs and small interfering RNAs], paving the way for rapid evaluation of their in vivo functions. Further, they

Patent Watch

A Shot of Ethylene in Your Coffee?

Next time you plunk down $4 for a cup of gourmet coffee, consider thanking the anonymous laborers who harvested the beans that went into it. The best coffees use hand picked beans, "because the fruits of a coffee tree do not ripen uniformly and, thus, there are both mature and immature fruit on the same tree," according to a new US patent (6,727,406).A dearth of cheap labor has forced many growers to adopt methods in which workers indiscriminately harvest beans from branches, ripe or not. Mechan

Software Watch

BNS Provides Faster Symbol Mapping

Biological databases typically tag their records with unique identifiers called accession numbers. These locators simplify record retrieval, but they are also database-specific, presenting a headache for bioinformaticians who want to map records in one database with their equivalents in another. Typically this is done manually, a tedious, error-prone task, especially when applied genome-wide.A few years ago, Robert Kincaid, a senior research scientist at Agilent Laboratories, Palo Alto, Calif.,

Tech Watch

Biomolecular Computing Gets a "Killer App"

© Nature Publishing GroupDespite buzzworthy applications such as cryptography and nanoelectronics, bio-molecular computing – the use of macromolecules such as DNA and enzymes to perform computations – will likely never match electronic computing in its speed and scalability. But a group of researchers, led by Ehud Shapiro of the Weizmann Institute in Israel, has found a promising "killer app" for biomolecular computing: molecular-scale diagnostics.1Using software programmed in g

Technology

Survival in the Microfluidics Market

Courtesy of Caliper TechnologiesImagine visiting the doctor's office for a routine annual checkup. Instead of drawing several vials of blood for analysis by an outside diagnostics lab, the doctor collects a single drop. Using a breadbox-sized instrument, she runs 20 or so tests in a matter of minutes and discusses the results with you before you leave. Meanwhile, a large pharmaceutical company down the road is using a similar, albeit larger instrument to analyze the biochemical properties of a m

Buyer's Guide to Protein Transduction Reagents

Six years ago, when John Tinsley's postdoctoral advisor at Texas A&Mtold him to find a protocol to introduce proteins into coronary endothelial cells, he couldn't find one in the literature. Tinsley tested a variety of commercial DNA transfection reagents, found one that worked for proteins, and has been using it since then.Tinsley's experience would be a lot different today. No longer must researchers rely on tedious and toxic procedures, or on proprietary reagents designed specifically for

Tools and Technology

A Brainy Twist to Image Analysis

Courtesy of DefiniensBromodeoxyuridine-stained tissue of mouse small intestine (original image, left; and Cellenger analysis, right). Cellenger has extracted whole crypts on a larger scale and distinguishes between mitotic and non-mitotic nuclei on a smaller scale.Propelled by the pharmaceutical industry, the high-content imaging field has experienced rapid growth, with several major new instrument releases in the past two years. High-throughput image analysis has lagged behind, however, because

Shrinking the Synchrotron

Courtesy of Lyncean TechnologiesAdvanced synchrotron radiation sources have revolutionized structural biology, allowing X-ray crystallographers to solve complex macromolecular structures. But as few of these soccer field-sized facilities exist worldwide, researchers have only limited access to them. Now researcher Ronald Ruth at the Stanford University Linear Accelerator Center has designed and is currently building a new desktop-sized synchrotron source called the Compact Light Source (CLS) tha

Affymetrix Breaks 100K Barrier

Courtesy of AffymetrixMicroarray giant Affymetrix http://www.affymetrix.com of Santa Clara, Calif., is raising the bar for whole-genome association studies. The first in a planned line of related products, the two-array GeneChip® Mapping 100K set can genotype over 100,000 single nucleotide polymorphisms (SNPs), 10 times more than its predecessor could.About half of the SNPs on the 100K set come from public databases. The rest stem from a proprietary database developed by Perlegen Sciences o

Data Points

Biotech by the Numbers

- Ken Kostel

Profession

Genentech Builds a Blockbuster-free Road to Billions

Courtesy of GenentechGenentech, the first US biotechnology company, has survived ugly patent disputes, product flops, and a Big Pharma partnership to become the biotech every company wants to be. The stock market value of the company, which makes the cancer drugs Herceptin and Rituxan, rose $7 billion (US), or 12%, in a single day in April based on promising data for a new lung-cancer treatment, Tarceva. That jump came less than a year after good results for Avastin in colon cancer trials sent t

Britain Fosters Bioincubators

Ned ShawIn the late 1990s, the UK Department of Trade and Industry began a program to boost highly skilled employment by financing biotechnology incubators. At the launch of the Biotechnology Mentoring and Incubator (BMI) Challenge, the United Kingdom could boast just two incubators, and as a part of the challenge the DTI awarded €4.9 million to 13 companies. The money went to incubators that provided lab space and equipment and also to organizations that provided just mentoring and manage

Science Rules

Germans Want to Save Animals by Suing Scientists

File PhotoA legal initiative is underway in Germany to give animal-rights organizations the standing to sue scientists and others who violate animal rights granted in a 2002 amendment to the German constitution. Animal-rights activists argue that the constitution offers no way of enforcing those rights. "Animal experiments have to be 'necessary' and 'ethically justified,' but those are vague legal terms," says Eisenhart von Loeper, an attorney and chairman of People for Animal Rights Germany. "T

Profession

How to Balance Short- and Long-term Research Goals

You do it already. You spend a portion of your research hours on the here and now, a slice or two on what's to come, and a sliver on the past. What you may not do is purposefully work out what the best balance is between past, present, and future. To preclude a nighttime visit from a hooded Ghost of Projects Yet to Come, a la Dickens, take some time to analyze your present allocation.If you define present projects as everything from bench work to publication, then future projects include brainst

Closing Bell

Lab Vultures

One day my adviser asked me to accompany him to an unoccupied lab whose former occupant had retired. It was like entering a well-appointed haunted house: glassware on the shelves, awaiting use; chemicals in the hood, fuming; gel boxes idling on the bench. It was a lab, but its eeriness was unsettling; it felt somehow wrong to be there without the owner. I was snapped out of my thoughts by my adviser, who turned suddenly and asked, "What do you think of this centrifuge?" Now I understood why we h

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