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Frontlines Image: Anne MacNamara The source of body asymmetry How can a developing body tell its right from its left? An ion pump creates a voltage gradient in embryos that is crucial in determining body asymmetry, according to a team of scientists at the Forsyth Institute and Harvard Medical School (M. Levin et al., "H+/K+-ATPase activity comprises an early step of left-right asymmetry during development," Cell, 111:77-89, Oct. 4, 2002). "We have identified a completely novel mechanism that functions in left-right asymmetry. It's a new toy for people to play with in terms of [determining] how the embryo figures out which side is left and which side is right," says Michael Levin, assistant member of the staff at the institute and assistant professor at the Harvard School of Dental Medicine. Asymmetry is important not only in determining the location of various internal organs such as the spleen and liver, but it is also crucial in the brain, notes Levin. Speech, for instance, is located in the brain's left hemisphere. Studying frog embryos, Levin and his colleagues found that the ion pump begins operating earlier than previously thought. The researchers observed a voltage gradient at the four-cell stage of Xenopus within about an hour and a half after fertilization. Researchers had believed that asymmetry begins at gastrulation, the developmental stage in which the embryo begins to form layers two cells thick. "This radically revises ... the current knowledge of when the embryo knows left from right," he says. --Harvey Black Image: Erica P. Johnson The new white paper for pharma An undergraduate chemist and two high-school students working at GlaxoSmithKline's Medicines Research Center in Stevenage, UK, have found a faster, cheaper, and easier way to do several reactions at once. Working with research leader Simon Macdonald, the students carried out a range of chemical reactions by simply pipetting ingredients onto cellulose chromatography paper (S.E. Shanahan et al., "The use of cellulose (chromatography paper) as a cheap, versatile and non-covalent support for organic molecules during multi-step synthesis," Chemical Communications, advance online publication, DOI:10.1039/b208083d). To monitor reaction progress, pieces are snipped off with scissors and analyzed. In two to three days, the students can determine which reactions worked. "Solid phase experiments can take so long that you're often no longer interested in the compounds you were originally trying to make," says Macdonald. The approach was inspired by the work of Norway-based SINTEF chemist Lorenzo Williams, who used glass-backed chromatography plates as the support. "It is the simplicity I find attractive," says Williams. "Any technology that can accelerate the drug-discovery process is of interest to the pharmaceutical industry." Another advantage is the cost: Chromatography paper purchased for just a few dollars should last for years. "The method complements solid-phase chemistry," says Macdonald. "It won't replace it, but we can use it as a rough and ready approach a 16-year-old student can do." The students now have their names on a scientific paper, and, Macdonald adds, they may be cited as coinventors on the forthcoming patent. --David Bradley "Iggies" 2002 Studying the genitalia of sculptures is a hard job, and no one necessarily has to do it, but at least Chris McManus is getting due recognition for his pioneering work. McManus and others were honored recently at the 12th annual Ig Nobel Prize Ceremony at Harvard University. Established in 1991, the Ig Nobels are presented annually by the science humor magazine, Annals of Improbable Research, which spoofs the Nobel Prizes by celebrating the unusual and imaginative in scientific achievements. Several Nobel laureates were on hand to recognize McManus's paper "Scrotal Asymmetry in Man and in Ancient Sculpture." Among other research recognized were definitive studies on belly-button lint, courtship behaviors between ostriches and humans, and the creation of a dog-to-human translation device. Theodore Gray, cofounder of Wolfram Research, Champaign, Ill., was awarded the Ig Nobel in chemistry for his construction of a periodic-table table. Needing a new table for his office, he built a table resembling the periodic table. Each element is represented by a tile with a cubbyhole housing a sample of that element. Gray was surprised but pleased by the recognition of his woodworking prowess. "Winning the Ig Nobel is the highest conceivable award this table could be eligible for," Gray says, "and it's also better than an office-supply catalog table." --Hal Cohen Photo: Courtesy of Doe Joint Genome Institute The sea squirt genome While creationists claim that the fossil record lacks transitional forms, genome prospectors are discovering many clues that link life. At the 14th International Genome Sequencing and Analysis Conference held in Boston on Oct. 2-5, Daniel Rokhsar, associate director of the Department of Energy's Joint Genome Institute in Walnut Creek, Calif., introduced a pivotal player in vertebrate evolution from their spineless ancestors--the sea squirt Ciona intestinalis. "These little sardine-like guys illuminate where we came from. They are our relatives, as icky as they might look," he said. Sea squirts occupy a branch of the evolutionary tree between echinoderms and vertebrates. "We've known for the last century that they are related to us in some way, and we can now look at that on a genomic scale," Rokhsar said. Despite the fact that these ocean-dwelling hermaphrodites collect food with mucus sheets and use a ganglion for brainpower, they have vertebrate-like rudiments of the thyroid, pituitary, and pineal glands. About 12% of the 15,500 genes have counterparts among vertebrates but not invertebrates, and 26% are unique to sea squirts. The animals do not synthesize certain molecules, including histamine, melatonin, and myelin, which are hallmarks of vertebrates, and they have single copies of some genes that expanded into gene families as vertebrates evolved. "The sea squirt represents an important branch point in prevertebrate evolution," said Edward Rubin, head of the Genome Sciences Division at Lawrence Berkeley National Laboratory in California. And with most of the genome sequenced, comparative genomicists should expect sea squirt data to start filling in evolutionary gaps soon. --Ricki Lewis Image: Anne MacNamara Rinse, spit, sequence Stash the swab; just gargle and spit. That's the idea behind a novel method for DNA collection being studied by University of Florida (UF) clinical scientist Julie Johnson. Instead of drawing blood or scraping the cheek lining with a small brush, researchers are using over-the-counter mouthwash to collect cells containing genomic DNA. Patients may no longer have to fear a needle prick, and scientists get an abundance of DNA to work with. "The gargling of mouthwash causes a small number of buccal cells to wash off," says Johnson, director of UF's Center for Pharmacogenomics. "From those, we can get enough DNA to do [as many as] 5000 experiments," whereas traditional swabs obtain enough for only a handful of studies. Johnson's team also found that the DNA collected is stable for prolonged periods at room temperature, indicating that samples can be safely stored and shipped without the need for special packaging such as ice (T.E. Andrisin et al., "Collection of genomic DNA by the noninvasive mouthwash method for use in pharmacogenetic studies," Pharmacotherapy, 22:947-53, August 2002). Phil Danielson, assistant professor of molecular biology at the University of Denver, says the mouthwash idea isn't new, but pressure in the forensic community to move away from drawing blood is now pushing the idea to the forefront. "Raw blood contains inhibitors of the PCR reactions we use to amplify DNA. The use of buccal cells from the mouth as a source of DNA avoids this all together," Danielson explains. --Kelli Miller Image: Erica P. Johnson With age comes $$$ National Institutes of Health officials recently reported at the annual meeting of the Association of Independent Research Institutes that older investigators are being awarded a larger share of grant money than in the past. According to their report, only 9.7% of the principal investigators receiving NIH money in 1980 were over 55. That percentage climbed to 20.4% in 2001. During that same time period, the percentage of primary investigators 35 or younger receiving NIH grants fell from 22.6% to 3.8%. Some have blamed the trend on the postdoc rut saying biological scientists spend more time collecting the necessary credentials to receive a tenure-track faculty position ("NIH awards to younger investigators declining, later exit from postdocs," The Blue Sheet, 45[37], Sept. 11, 2002.). Others interpret the numbers differently. Gene Cohen, a George Washington University professor and director of the Center on Aging, Health and Humanities, says more people are shunning full retirement in favor of continuing to work in some capacity. It's an embraceable trend, he says. Cohen adds that older scientists usually remain productive. Studies have found that while their publications diminish, what they do write is cited more often. Cohen attributes that to work seasoned with a lifetime of experience, perspective and years of working in one area. "It is very different--what is happening to what has been called the retirement years," he says. The rocking chair, lemonade, and warm milk "is an ancient fairy tale. Today the focus is on potential." --Bob Calandra

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