May 2004

This issue of The Scientist focuses on biosecurity. More specifically, it deals with the handling and detection of select agents, a catalog of about 80 bacteria, viruses, fungi, and toxins that US authorities have identified as particularly high-risk. See page 12 for a primer.Select agents divide the US research community like few other topics. Regulations for their transport and handling are considered either prudent or draconian, a minor inconvenience or a grave impediment, depending on who yo

Brad FitzpatrickScience and technology have been enlisted in the fight against terrorism. The US Department of Homeland Security is investing over $1 billion per year in R&D. The National Institutes of Health is devoting even more, nearly 6% of its $28 billion R&D budget. US universities, national laboratories, and industrial R&D establishments all have become involved. While the nation is calling on the scientific community to serve these vital missions, it is also implementing poli

Janet Ginsburg's article was timely, informative, and sobering.1 It confirms my worst fears, after 10 years of work in a futile effort to reform the live-animal food markets in the Chinatowns of San Francisco, Los Angeles, Oakland, and elsewhere. Conditions are nearly identical to those of the Chinese markets whence came the recent SARS outbreak: people living in over-crowded, unsanitary conditions cheek-to-jowl with animals of all kinds, both wild and domestic, a disaster in the making.The mark

You propose a rational idea to increase the efficiency of scientific research. It is a good one.1 The current focus on grants is destructive, because the fruits of our labor are understanding and dissemination of knowledge. Grants are but a weak surrogate for this activity. Thank you for writing a highly lucid and informative article. We hope it opens a dialogue.George Perry and Mark Smith George Perry, PhDProfessor, Institute of Pathology Case Western Reserve University george.perry@case.eduI e

It was during a walk along the coast that Ravi Naidu found the answer to his problem: "Seaweed! The idea just popped up." The ubiquitous and cheap plant material held the solution to his biore-mediation experiments DDT-contaminated soils. He and colleague Mallavarapu Megharaj of the University of South Australia found that sodium enhances bacteria's ability to degrade DDT in anaerobic environments. Throwing in some organic matter as fertilizer further accelerated the process. "Seaweed contains s

Discerning whether a biological threat comes from terrorism or an emerging infectious disease is one problem that researchers at the Courant Bioinformatics Group at New York University (NYU) want to solve. Bhubaneswar Mishra's multidisciplinary team has created a series of complex software programs that allow researchers who deal with intricate, real-world bioinformatics problems to develop their own algorithms. This allows them to use mathematics to solve real issues in biology.With one interac

Of the 376 survey participants, 79% believe there is a moderate or greater chance of a bioterrorist attack occurring somewhere in the world in the next five years. And, 81% believe there is moderate or greater justification for the increasingly large sums spent by governments on research aimed at preventing and mitigating the effects of such an assault.But 46% feel that government spending on bioterrorism research is diverting monies from more important investigative areas, and 19% state that th

1. What's so select about select agents?Various US agencies, including the Department of Health and Human Services, deemed more than 80 types of bacteria, viruses, fungi, and toxins as "select agents" after Sept. 11, 2001. These hazardous substances, biological and chemical, were chosen for their threat to the health of humans, animals, and plants. The Centers for Disease Control and Prevention (CDC) allowed scientists to comment on the proposed list and made appropriate changes before finalizin

Reprinted from T.D. Brock, Robert Koch: A Life in Medicine and Bacteriology, Science Tech Publishers: Madison, WI, 1988, pg. 51, Fig 6.5Robert Koch (1843–1910) was a country doctor from the German hinterlands of what is now Poland. He liked to investigate samples from his barnyard animals under a microscope. He went on to become the world's first and one of its greatest bacteriologists, winning the Nobel Prize in 1905. Although famed for his work on tuberculosis and the postulates named af

What was the genesis of the Public Library of Science?Courtesy of Harold VarmusA conversation with Pat Brown in San Francisco in December 1998, a year before I left the NIH, about the open-access preprint archive that physicists had set up at Los Alamos National Laboratory got me thinking for the first time about open-access publishing in biology and medicine. The Public Library of Science began as an advocacy group for the NIH archive, PubMedCentral, about a year after I left the NIH. Subsequen

Compiled by Christine Bahls cbahls@the-scientist.com and Maria W. Anderson manderson@the-scientist.com

© Dr. Tony Brain/Photo Researchers, Inc.Plasmodium parasites have ravaged humanity for centuries, decimating young people, and fixing alleles like that for sickle cell in populations at risk. Today, listed in a trinity with tuberculosis and AIDS as the most significant of the world's health problems, malaria infects 300 million to 500 million people each year and kills more than one million. Efforts to understand the malaria parasite and the mosquitoes that spread it are aided in part by ge

RNA SWITCH:©2004 Nature Publishing GroupThe GlmS enzyme, which is involved in GlcN6P synthesis, is translated from mRNA containing a ribozyme sequence. GlcN6P activates the ribozyme cleaving the mRNA sequence and turning enzyme production off. (Redrawn from T.R. Cech, Nature, 428:263–4, 2004)Coming from various directions, a number of research groups stumbled upon a naturally occurring mechanism for gene control that depends solely on RNA and environmental cues. Though the working det

SYNAPTIC MITOCHONDRIA:Courtesy of Husseini ManjiThe surge in intracellular calcium during an individual action potential is rapidly buffered by mitochondrial calcium uptake. The release of calcium back into the cytoplasm is believed to allow for post-tetanic potentiation. ATP-production is essential for vesicle docking, fusion and endocytosis. Mitochondrial pathology and some treatments affect the mitochondrial membrane potential. Disrupting the MMP results in more pronounced calcium spikes; cha

FIRST BITE:Courtesy of CDC/Jim GathanyFemale Anopheles gambiae mosquito feeding.A decade ago, scientists around the world recognized that despite malaria's tremendous disease burden, research on the topic had stagnated. With funding at low levels, robust molecular biology tools numbered few. Today, genome sequences for Plasmodium falciparum, the parasite causing malaria, and for Anopheles gambiae, the mosquito that spreads it, have already fundamentally changed the research landscape. Plasmodium

Paul H. SilvermanCourtesy of Paul H. SilvermanFor more than 50 years scientists have operated under a set of seemingly incontrovertible assumptions about genes, gene expression, and the consequences thereof. Their mantra: One gene yields one protein; genes beget messenger RNA, which in turn begets protein; and most critically, the gene is deterministic in gene expression and can therefore predict disease propensities.Yet during the last five years, data have revealed inadequacies in this theory.

Autoacetylation has neither the history nor the reputation of autophosphorylation, but the phenomenon may pull some weight. Researchers led by Philip Cole at The Johns Hopkins University School of Medicine confirmed that autoacetylation of the p300 histone acetyltransferase (HAT) leads to a greater than 10-fold acetylation activity enhancement.1Cole's group demonstrates that a novel autoinhibitory loop serves as a pseudosubstrate that otherwise prevents endogenous substrates from docking within

The body's response after a spinal cord injury often causes collateral damage, including cell death and ultimately paralysis. German researchers, funded by the Christopher Reeve Paralysis Foundation, report that they have discovered at least one weapon the body may use against itself: the cellular membrane-bound ligand known as CD95L or FasL.In mice, blocking this ligand with antibodies after severing the spinal cord preserves oligodendrocytes and neurons and promotes axonal regeneration.1 This

© James Newhouse, Maqsudul AlamProteins possibly used for oxygen sensing in primitive organisms appear to be hemoglobin ancestors. Microbiologist Maqsudul Alam at the University of Hawaii and collaborators at the University of Texas (UT) Southwestern Medical Center at Dallas found a "protoglobin," a hemoglobin progenitor, in Aeropyrum pernix, an aerobic organism that lives in near-boiling salt water. They also found the protoglobin in Methanosarcina acetivorans, an anaerobe found in lake-bo

©2004 Elsevier ScienceScientists can now watch the mouse brain in action thanks to a new technique that lights up specific populations of neurons as they fire.1 Because the fluorescent marker responsible is genetically encoded, it now will be possible to follow an animal throughout its life to see how activity changes during development and learning, says neurobiologist and coauthor Matt Wachowiak of Boston University.Wachowiak and colleagues targeted a pH-sensitive fluorescent marker calle

One traditional gene-therapy method relies on homologous recombination. The desired gene segment is placed on a small plasmid and delivered by virus or liposome, but this approach has variable expression levels and instability, and is limited by a small insert size. Yeast artificial chromosomes circumvent some of these problems, but YACs cannot be propagated in mammalian cells. Now a team of scientists at DNAVEC Research of Ibaraki, Japan, has come up with a solution: They have developed a metho

Proteomicists who want to share their data, take heed: A team at the University of Alberta has a software tool for you. GelScape https://www.gelscape.ualberta.ca is a free, cross-platform, browser-based tool for annotating, manipulating, comparing, and storing 1-D and 2-D protein images.1 Users can run the Java-based software off servers in Edmonton or install a local copy on their individual PC, according to David Wishart, a bioinformatics professor at the University of Alberta who oversaw the p

A GRADIENT OF PORE SIZES:Courtesy of Michael J. Sailorimparts a rainbow of colors to a porous silicon chip, one of a variety of new biosensor technologies in development around the world. The different colors correspond to different sized pores, ranging from a few nanometers to hundreds of nanometers in diameter. These pores help the device discriminate and detect proteins and other molecules based on their size.One morning in March 1995, the deadly nerve gas sarin wafted through the Tokyo subwa

Researchers seeking a new ultraviolet spectrophotometer face no shortage of choices. Since making their first appearance on lab benches more than 60 years ago, UV specs have expanded and morphed into instruments that can handle a breadth of research applications, from the simplest single-wavelength measurements to high-performance, multispectrum analyses. Scientists must therefore keep their laboratories' specific needs in mind when making their choices. Features to consider include the intended

Courtesy of Quantum DoWhen it comes to gene-expression analysis, researchers seem always to be sacrificing something. With real-time quantitative PCR, it's gene number: Though inexpensive enough to apply to large numbers of samples, each assay can test, at best, three or four transcripts simultaneously. Microarrays, on the other hand, sacrifice sample throughput, probing tens of thousands of genes in a single sample.Quantum Dot https://www.qdots.com has developed a compromise solution. According

Recent probes of the dynamic nature of chromatin have revealed that this structure is more than a simple genomic packaging tool. Indeed, chromatin remodeling plays a role in regulating processes such as transcription, replication, repair, and epigenetic silencing. Understanding how chromatin's structure responds to histone modifications and how transcription factors bind to DNA in chromatin in vivo can reveal much about transcriptional regulation.Studying protein-DNA interactions in a native chr

Courtesy of GT VisionHistologists and pathologists examining slide after slide each day now have a new tool to ease their microscopy headaches and dramatically increase their throughput as well. Surveyor, an automated imaging system from Frederick, Md.-based GT Vision https://www.gt-vision.com scans whole sections at 25 fields of view per second. The system includes a motorized microscope stage, high-specification workstation PC, and camera, according to company literature.Users view slides on a

Courtesy of ESAWhen it comes to metabolomics, there can be such a thing as too much information. The blossoming science typically uses mass spectrometry and nuclear magnetic resonance (NMR) to hunt for specific metabolites as markers of abnormal biological processes. "But those devices aren't geared to analyze samples like serum or urine that may have thousands of individual components," says Paul Gamache, director of applications development for ESA https://www.esainc.com in Chelmsford, Mass. "T

The portion of the US budget dedicated to biodefense spending has proved difficult to track since 2001. Expenditures are spread out among several agencies and are often combined with defense and pre-paredness initiatives for chemical or nuclear threats. The National Institute of Allergy and Infectious Diseases (NIAID), one of the few agencies with a biodefense line-item, has seen that part of its budget grow dramatically over the past several years. In addition, the nation's network of Biosafety

Courtesy of Pedro ScassaValley Fever, a pneumonia-like lung disease that strikes 50,000 people each year, has become an epidemic in southern Arizona, and John Galgiani, director of the University of Arizona's Valley Fever Center for Excellence in Tucson, wants to know why. But the research that might help this microbiologist uncover the state's Valley Fever mystery has been brought to a halt by the very agency, the Centers for Disease Control and Prevention, charged with protecting people from d

Courtesy of the CDCThe September 11 attacks and five anthrax-related deaths later in the fall of 2001 made it clear that the United States was vunerable to terrorist actions. Those events also caught the nation immediately short of the high-level biocontainment lab space needed to develop antibioweapon vaccines and drug treatments.Since then, the US Congress has approved plans for the National Institutes of Health to spend as much as $500 million on new biosafety space over the next few years,1

Ned ShawImagine an entertaining evening out on the town and talking science. Sound unlikely? Not to attendees of science cafés in Europe, North America, and Australia. Perhaps these comments, collected from Australian audiences, will sway naysayers to look more closely: "I love the exchange of ideas." "Provocative and fun." "I like seeing the 'techos' come out of the closet."Science cafés aspire to promote discussion of science in a community setting. Held in venues ranging from caf

File PhotoA rampant infection of "benchitis" has spread through my body. You might not have heard of this malicious disease but you'll probably recognize the symptoms. An infected individual comes in late, goes home early, sits for hours in front of the computer e-mailing friends, or makes comments such as, "If I have to run one more gel today I'm going to go crazy!"It's been my experience that a postdoc needs to have a lot of self-motivation to succeed. So much rests on what we can accomplish o

File PhotoLife in the laboratory can seem increasingly rule-bound, especially in these high-security times. In studying what makes life scientists tick, some researchers suspect that the most important decisions fall into the gray areas between the rules, leaving scientists groping for guidance."If you were to go into a laboratory and just watch for a month ... you would probably find a whole culture governed by rules that are largely not written down at all," says Nick Steneck, a University of

On January 20, I joined the ranks of those who've sacrificed themselves for science: I started one of those "low-carb" diets. So far, the sacrifice has been worth it.I'd always resisted celebrity-sponsored diets, smugly thinking my background in genetics and biochemistry made me more of an authority on matters nutritional than the likes of Whoopi Goldberg and Sarah Ferguson. I've even taught the subject.But this low-carb diet is different. It prescribes "good carbs and good fats" while blacking