August 2003

In this issue we take a close look at DNA microarrays, the current amore of biological and biomedical researchers. There's little reason to doubt that the infatuation will continue, at least for awhile. Microarrays are relatively inexpensive, powerful tools for assessing gene expression. On glass or plastic slides, thousands of known DNA sequences are printed, spotted or synthesized. mRNA is isolated from samples, often converted to cDNA and amplified, before hybridization on the slides. The

It is well known that the distribution of citation counts is highly skewed, with a few scientists receiving many citations but with most receiving very few. What is less well known is that when these counts are aggregated by institution, and then by place, these distributions become even more extreme, with most citations being associated with individuals in a small number of institutions in an even smaller number of places and countries. To demonstrate this geographical concentration, a sour

Selling Science Richard Gallagher's commentary1 focuses on doing a better job of selling science to the layman, so that the scientific community can continue to pursue its various interests. Doesn't marketing science like a new model of automobile, by identifying "members of the research community who are knowledgeable about the issues, sympathetic to them, and confident in front of a camera," strike anyone as a bit bizarre? The ethical and moral implications of one's work should not be seen

No Dignity in Poverty Asma Asyyed's story1 is very familiar to me because it is also my own. I am still a postdoc and up until recently I felt very happy doing science. There was a certain joy that was removed from worldly concerns... of discovering, or pursuing something truly beautiful as a research problem, or simply thinking about the implications of my work (I work on nerve regeneration/spinal cord injury). Never mind being poor, never mind that I worry about my family's and my needs co

Begging Your Pardon, Ma'am The article title to your recent Frontline1 is an obvious derivative of "wham, bam, thank you ma'am." I was highly offended that you would think that this phrase is appropriate for your issue. This phrase has a derogatory sexual connotation that no person with good manners would bring up in polite conversation. How could you think that your readers, especially women, would NOT be offended by this? This article title brings journalism to a new low. Please hire mor

A Professional Resource I am a public affairs consultant. Some of my clients are Biotech companies and Genome geniuses. I started receiving your publication as a professional resource to keep up to date on a sense of the community and what you consider "breaking news." I do want to say just how much I enjoy reading the magazine. It is direct, contemporary and tongue-in-cheek at times with your own industry. Even the most technical articles have a readability level for a "commoner" like myse

Awareness Research First, I was glad to see Christof Koch1 and others interested in awareness incorporating the experimental methods of behavioral psychology (rather than to the over-hyped and conceptually bankrupt cognitive psychology). Second, I read with interest that Koch has turned his attention to individual nerve cells. In that regard he might want to check out the work (e.g., by James Belluzzi, Larry Stein and Bao Xue)2 on the operant conditioning of individual neurons. What we ca

UNESCO and the Genome In regard to the article about UNESCO,1 what was not included was the UNESCO Scientific Coordinating Committee for the Human Genome Project, which I had the honor to chair from 1988 to 2000 and which was abolished with the change of Director General. The UNESCO Scientific Coordinating Committee organized some 52 meetings and workshops. It carried out some five large South-North meetings in China, India, Mexico, Brazil and Namibia, and in combination with TWAS granted

Y Not Wonderful bit of history in your article. Wonderful bit of sociology in your article. Wonderful bit of political incorrectness in your article. And a wonderful perspective on science as we play with it. Please continue. William G. Reiner Associate Professor University of Oklahoma Health Sciences Center Oklahoma City, OK william-reiner@ouhsc.edu 1. R. Lewis, "Y Envy," The Scientist, 17[15]:64, July 28, 2003. function sendData() { document.frm.pathName.value = location.pathname;

Snapshot | The Eclectic Reading Habits of Scientists When it comes to reading nonscientific books, the interests of our readers would fill a library. The 322 readers who completed our survey have books on fly fishing, science fiction, politics, and philosophy, sitting on their coffee and bedside tables. One reader has a self-described "voracious" appetite: "I usually have at least three books going at all times." They also read newspapers: 62% do so on a regular basis, with the New York T

Foundations | The First Array Courtesy of Mark Schema Ron Davis and I were studying plant transcription factors in 1990, but progress was slow and arduous because the gene expression tools were so primitive. We conceived of the DNA microarray in 1993 to speed up gene expression analysis by combining biology and high technology. We adapted Affymetrix VLSIPS technology to synthesize yeast microarrays, and measured gene expression in yeast cells by hybridizing fluorescent probes derived from

First Person | Paul Herrling Courtesy of Ruder Finn When Paul Herrling didn't do his homework at his Swiss boarding school, the facility's science-loving director devised unusual punishments. The then-teenaged Herrling, now Novartis' head of corporate research, had to catalog the man's collection of crickets, which the director had recovered from ice, ages old, on a nearby Italian mountain. "He was studying glacial repopulation," says Herrling. The discipline, and the fervor of the direct

Science Seen | R2DADA Courtesy of University of Western Australia  This robotically drawn artwork took some doing to produce. First, scientists at the Georgia Institute of Technology cultured individual rat neurons and attached anodes to them. Then, the random nerve impulses were sent directly to a robot at the University of Western Australia in Perth, which drew lines with each impulse. These drawings were entered in numerous art exhibits. But no robot should quit its day job. Not yet,

So They Say "We believe that a defect in [the gene] may make one supersensitive to dopamine, somewhat like being born on cocaine." --Psychiatrist John Kelsoe, Veterans Affairs San Diego Healthcare System, on his team's discovery of a genetic basis for manic depression. From the San Diego Union-Tribune "I need your word you are not going to publicize full frontal pictures of this tree." --Jared Milarch, Champion Tree Project, addressing volunteers who helped him clone Methuselah, the wo

5-Prime | Demystifying Mass Spectrometry What is mass spectrometry? Mass spectrometry, or MS, is the measurement of molecular mass that is gained by determining the mass-to-charge ratio (m/z) of ions generated from the target molecule. Mass spectrometers are comprised of a source for generating the ions from the sample and delivering them into the gas phase; an analyzer for separating and sorting the ions; and a detector for sensing the ions as they are sorted. An MS "run" generates a spec

September Calendar Click to view enlarged September calendar (250K) --Compiled by Christine Bahls(cbahls@the-scientist.com) function sendData() { document.frm.pathName.value = location.pathname; result = false if (document.frm.score[0].checked) result = true; if (document.frm.score[1].checked) result = true; if (document.frm.score[2].checked) result = true; if (document.frm.score[3].checked) result = true; if (document.frm.score[4].checked) result = true; if (!result) alert("Plea

In 1992, American writer Andrew Solomon, then in his late-20s, was about to publish his first novel when he unexpectedly slid into a major depression. In a subsequent book, he wrote that the experience is "almost unimaginable" to the uninitiated. Describing it, he likened himself to an oak being strangled by a vine, "a sucking thing that had wrapped itself around me, ugly and more alive than I." He called up the image of falling into an abyss: "You hit invisible things over and over again, un

Source: Chart created by Eugene Garfield (egarfield@the-scientist.com), founding editor of The Scientist, and Soren Paris. The Historiograph is a chronological linkage map that visualizes the genealogy of the microarray literature. Starting with the Pat Brown group in 19951 (Also, see Foundations) it progresses to analysis, review and implementation in the ensuing years. The 13 key papers are identified through their citation links. Most have been cited highly in the literature and heavily ref

Courtesy of Gary Churchill  THE GOOD, THE BAD, AND THE FILTERED: At left is a poor quality microarray with problems due to background contamination. At right is a good quality microarray with well defined spots and low background intensity. Data preprocessing methods can normalize and filter data derived from such images, which may make it impossible to detect problems apparent in the raw image data. Since their rise to fame in the mid 1990s, microarrays have been both lauded and critici

Courtesy of Roderick MacKinnon, Rockefeller University Playing gatekeeper to human health, channel proteins penetrate all cell membranes. In the nervous system, armies of channels open and close in precise order to create action potentials, the brief membrane depolarizations that act as the primary form of electrical signaling in animals. These action potentials prove so enduring, functioning properly even in extreme experimental preparations, that investigators might consider ion channels in

Courtesy of Declan Doyle  THE POTASSIUM TURNPIKE: KirBac1.1 in a membrane of a cell (green) ready to conduct potassium ions (yellow). Until recently, little progress has been made in determining high-resolution structural data for membrane proteins--the transporters, channels, and receptors that play critical roles in cell physiology. Now, scientists say they might be seeing the trickle that precedes the deluge. The current explosion of genomic information has led to the identification o

Copyright Jurgen Berger, Electron Microscopy Unit, Max Planck Institute Recent research on Arabidopsis thaliana flowering may sow the seed of new connections between plant and human reproduction. Gordon Simpson and Caroline Dean at the John Innes Center in Norwich, UK, recently published work with implications far beyond the plant science field. Their work also builds a basis for understanding alternative polyadenylation--a much ignored cousin of alternative splicing that helps explain how a 3

Courtesy of Mark Jenkins  SLICED MICE: Single-cell-thick sections of adult mice expressing CD45.1 stained with nuclear dye (blue) and a monoclonal antibody specific for CD45.2 (red). The left panel shows a background level of CD45.2 staining. The center panel shows a mouse that received several million Salmonella peptide-specific CD4 T cells from a transgenic mouse expressing CD45.2. Transferred naïve T cells were found only in secondary lymphoid organs. At right, when also injected w

SOFTWARE WATCH | Map Protein Interactions Click to view enlarged map (26K) When Laurent Cocea lost his job in 2002, he immediately set to work creating his own company to solve a problem he had while still employed at Amgen in Toronto. "We had a team of students who spent six weeks mapping protein interactions," he says. "Once they did it, they couldn't edit it." Now, thanks to "Dynamic Signaling Maps," a program Cocea designed, any researcher can map complex protein interactions in minute

Courtesy of Thermo Electron For years, mass spectrometry has been de rigeur in chemistry labs. Recently, though, it has become a mainstay of proteomics research, too. Two years ago, investment bank UBS Warburg identified proteomics as the fastest- growing application of mass spectrometry, a prediction borne out at this year's American Society for Mass Spectrometry (ASMS) annual meeting, where more than 1,100 of 2,227 presentations discussed some aspect of proteomics. It took a confluence of t

Courtesy of the Institute for Systems Biology  MOVING FORWARD: The LCQ Deca XP, an electrospray ionization/ion trap mass spectrometer from Thermo Finnigan The sheer number of new protein-focused mass spectrometry (MS) instruments introduced last year is a testament to the growing importance of the technique in proteomics research. Coupled to this trend is a growing need for automation of upfront sample preparation to feed these analytical machines. From the specialized academic lab to hi

For biologists, DNA microarrays present at once unprecedented opportunities and monumental challenges. In the opportunities column, microarrays produce genome-wide gene expression snapshots, facilitating a migration from gene-by-gene hypothesis-driven research to a relatively unbiased "discovery mode." The challenges broadly include data quality, analysis, and interpretation--that is, reaching an accurate and useful biological conclusion from the correlations identified within the data. Prog

Images courtesy of Meltec First came genomics, then proteomics. Next up: functional proteomics, a strategy aimed at understanding the relationships between cellular proteins. One such state-of-the-art technology is MELK, a patented "topological proteomics" approach from Meltec in Magdeburg, Germany. MELK, or multiepitope-ligand kartographie, combines cell biology and biomathematics to visualize three-dimensional protein networks of intact cells at the cellular and subcellular levels. By obser

Courtesy of Amersham Biosciences Whole-genome amplification (WGA) can replenish dwindling stocks of genomic DNA or bolster low yields, which limit the number of downstream assays that can be completed. PCR-based WGA methods can introduce amplification bias and generate products of insufficient length for some applications, such as RFLP analysis. To alleviate this problem, Amersham Biosciences of Piscataway, NJ, released in April the GenomiPhi™ DNA Amplification Kit, a non-PCR-based meth

Courtesy of Pierce Biotechnology Pierce Biotechnology has expanded its repertoire of protein chemistry products with the new ProFound Protein Interaction Mapping Kit, which helps researchers to pinpoint where protein partners come together. The technique takes advantage of a unique cleaving agent and bypasses the need for more complex approaches such as nuclear magnetic resonance or X-ray crystallography, says Patti Domen, a senior research scientist who designed and tested the product at Pie

TIP TROVE | Plan Your Research to Build a Career Courtesy of Julius Axelrod It can be advantageous to join a laboratory that is somewhat crowded so you can spontaneously interact with your colleagues, but try to avoid working on trivial or incremental problems that come from working in large teams. Also, avoid fashionable fields of research that are highly competitive; many problems are important but neglected. Do not spend long periods of time on researching problems that are not going any

Courtesy of Amy Sillman If you are a postdoc, you are probably writing something: a fellowship application, an abstract, an article, or something for your principal investigator's (PI) grant. Your first major introduction to scientific writing was probably in graduate school, when you were expected to produce a dissertation, and maybe a couple of publishable articles along the way. I remember well that time in my life. At first it was really cool to be working on the dissertation, after passi

File Photo Like their colleagues in private industry, academic researchers need to think defensively when it comes to the use of research materials covered by patents. Many university-based scientists may have systems in place already to document the equipment and materials used for experiments related to research financed by commercial sponsors. It is up to the company sponsoring the work to ensure that technology is licensed and the royalties paid. But a drawn out legal battle has ended in

Courtesy of Adriano Aguzzi Early Indication: I was fascinated by life sciences in high school. Medical school failed to provide me with sufficient background knowledge in the natural sciences to successfully pursue a career as a scientist, so I engaged in all sorts of extracurricular activities in laboratories while I was a medical student. How I Got Here: My medical background proved very useful for research activity in the neurosciences, which has become my mission in the last 15 years. Wh

Advances in technology always make us uneasy. Telephones, vaccinations, E-mail, mobile phones--despite the value we now place on them, these innovations provoked dire forecasts, and damnation, on their arrival. A vocal minority continue to see these innovations as dangerous. Some of the unease that comes with the new and different is well founded. We don't have to search far to find examples of new technologies that turned out to have unanticipated, troublesome consequences. Nonetheless, muc