Notebook

TIGHAR/P. Thrasher Tom King, senior project archaeologist for TIGHAR, excavates a site on Nikumaroro Island in 1997. In 1991, TIGHAR archaeologists found a shoe heel marked "Cat's Paw Rubber Co. USA" (right). They suspect that the heel and other matching shoe parts they found belonged to Amelia Earhart. STILL SEARCHING Lady Lindbergh may not have met her demise in the waters of the Pacific after all. On Dec. 4, 1998, at the annual American Anthropological Association (AAA) meeting in Philadelphia, historians and anthropologists associated with The International Group for Historic Aircraft Recovery (TIGHAR), a nonprofit research, educational, and historic preservation organization based in Wilmington, Del., presented this theoretical scenario for the disappearance of Amelia Earhart and her navigator, Fred Noonan: In 1937, the two crash-landed in the Republic of Kiribati on what's now Nikumaroro Island, a then-uninhabited Polynesian island 400 miles southeast of Howland Island, Earhart's intended final destination. In 1938, members of a work party placed on the island by the British government found human remains that were then taken to Suva, Fiji, by British colonial officials and examined by D.W. Hoodless of Suva's Central Medical School. Although the British suspected at the time that the 13 bones found might belong to Earhart, they decided to suppress the discovery for fear of spreading unfounded rumors. When Hoodless concluded that the bones belonged to a short, stocky male, British officials abandoned the investigation--unaware, apparently, that Earhart had flown with a male navigator. They also discounted a sextant box found near the site since the old-fashioned nautical sextant found inside would not, they reasoned, be among the equipment of an aerial navigator in 1937. Apparently they didn't know that Noonan, a former sea captain, frequently carried such a device. TIGHAR members effectively reopened the case in 1991 when, while conducting test excavations, they found shoe fragments later confirmed to be those of an American-made women's shoe. Based on a photograph of Earhart taken 10 days before her death, the size of the shoe is about the same as hers--although some dispute this, saying that shoes known to belong to Earhart are a good deal smaller. As for the evidence found in 1938, both the box and the bones have been misplaced and perhaps destroyed. Hoodless's papers, however, were uncovered, and in 1997, at TIGHAR's request, forensic anthropologists Karen Burns of the University of North Carolina and Charlotte and Richard Jantz of the University of Tennessee reexamined the measurements and notes taken by Hoodless. Using FORDISC 2.0, an interactive computer program for the classification of unknown adult crania according to race and sex, they both concluded independently that, contrary to Hoodless's conclusions, the bones most likely belonged to a European female who was between 5 feet 6 inches and 5 feet 9 inches tall--which is in agreement with the reported height of 5 feet 8 inches on Earhart's pilot's license application. Of course, this, even with the shoe evidence, is by no means conclusive. "Circumstance, coincidence--yes," TIGHAR Executive Director Richard E. Gillespie said of the collection of evidence presented at the AAA meeting. "But it's piling up, and the piles are getting pretty deep." Finding the original bones in Fiji or additional bones at Nikumaroro is unlikely, as is retrieving a sufficient amount of DNA to definitively show that the bones are Earhart's or Noonan's. But TIGHAR will try to do just that when they return to Nikumaroro for another expedition scheduled for the spring of 2000. GENES AND AIDS Some genes slow the progression of AIDS in persons infected with HIV; others speed it up. So says a series of studies by a group at the Laboratory of Genomic Diversity at the National Cancer Institute (NCI). Three studies in the past two years have associated three genes--each with three alleles--with a deceleration of AIDS onset. The first paper reported a structural mutation in the middle of the CCR5, or CKR5, gene (M. Dean et al., "Genetic Restriction of HIV-1 Infection and Progression to AIDS by a Deletion Allele of the CKR5 Structural Gene," Science, 273 :1856-62, 1996); the second reported a mutation of the CCR2 gene (M.W. Smith et al., "Contrasting Genetic Influence of CCR2 and CCR5 Variants on HIV-1 Infection and Disease Progression," Science, 277 :959-965, 1997); and the third identified the apparent effect of a gene called SDF-1 (C. Winkler, "Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant," Science, 279 :389-93, Jan. 16, 1998). A fourth study out last month associates accelerated AIDS progression with a particular variation in the promoter region of CCR5 (M.P. Martin et al., "Genetic Acceleration of AIDS Progression by a Promoter Variant of CCR5," Science, 282 :1907-11, Dec. 4, 1998). While investigators are unsure of the mechanism that causes the CCR5 promoter region to speed up disease onset, they hypothesize that it somehow increases the number of available cell portals for HIV to infect. "We have indirect evidence that that's going on," says Stephen J. O'Brien, head of the Laboratory of Genomic Diversity. His group is currently looking for nuclear proteins that bind to the promoter region and act as transcription factors that can differentiate between the two alleles of CCR5. O'Brien cites two major applications for the findings. By reinforcing the notion that the CCR5 gene and its protein product are critical for HIV disease progression, the study suggests that interfering with the interaction between virus and host is a novel avenue for anti-HIV drugs (P. Smaglik, "Chemokine Advances May Provide New HIV Therapies," The Scientist, 12[5]:9, March 2, 1998). "Instead of targeting this moving virus target, which is mutating at a rate of a billion new mutations every day, you are targeting ... a fixed target, which is the specific cellular collaborators if you will, the parts that the virus co-opts to use." Researchers will attempt to, for example, develop chemokines that block HIV infection by interfering with the virus's cellular interaction. A second application will be to better monitor vaccine trials; scientists will be able to better gauge how much of the acceleration or protection they observe in subjects is due to the vaccine itself, and how much is the result of normal genetic differences. David Djicher & GE Sun Jurrassic Angiosperm Jeff Fage/Univ. of Fla. David Dilcher A ROSE BY ANOTHER NAME? The Yixian Formation around Beipiao, northeast of Beijing, electrified paleontology recently with its exquisitely preserved feathered dinosaurs, early birds, and other animals (J. Wang, "Scientists Flock to Explore China's 'Site of the Century,'" Science, 279 :1626-7, March 13, 1998). Now botanists are excited too with the discovery of what appears to be the earliest angiosperm. The flower characterizes this most successful of all plant groups, but the carpel, a leaflike organ enclosing the ovules or immature seeds, is the critical diagnostic feature (angiosperm means seed in a vessel). In other seed plants (e.g., pine cones), the ovules are exposed. And carpels are just what a joint China-U.S. team found in a slab of Yixian limestone (G. Sun et al., "In Search of the First Flower: A Jurassic Angiosperm, Archaefructus, from Northeast China," Science 282 :1692-5, Nov. 27, 1998). The age of the fossil, dubbed Archaefructus (ancient fruit), is still uncertain (122 or 145 million years), but either date qualifies it as the oldest angiosperm. The carpels, arranged helically along a pair of 8-cm stems, matured into fruits before they were buried, but still retain a stigma, the specialized floral surface that captures pollen. Each carpel contains two or three seeds. By enclosing the ovules, plants protected them from the environment and opened the way to coevolution with animals carrying pollen from plant to plant. "This was a major event in the whole vegetation of the Earth because of the success of flowering plants in managing outcrossing," says team member David Dilcher of the Florida Museum of Natural History, Gainesville. They were "now in control of their own pollination." But the ramifications don't stop there: mature carpels in the form of fruit became a food source for animals, thereby dispersing the seeds. That made possible the success of mammals, including humans. Dilcher hopes to find other specimens: "we're looking for the rest of the flower ... and hoping to fill in the gaps." DIPHTHERIA TOXIN PRODUCTION An X-ray crystallographic image of diphtheria toxin production suggests a new type of antimicrobial therapy (A. White et al., "Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex," Nature, 394 :502-506, July 30, 1998). When certain transition metal ions are present, they bind to a two-dimer repressor protein, called DtxR, that sits on the toxin gene. "The Corynebacterium diphtheriae toxin gene is carried by a phage that infects the bacteria. When the bacterium has nutrients, no toxin is produced," explains Dagmar Ringe, a professor of biochemistry at Brandeis University's Rosenstiel Basic Medical Sciences Research Center. But when the immune system responds to infection by sequestering iron, the metal ions pop off the repressors. The rush of toxin kills nearby cells, releasing nutrients, and also damages the heart and nervous system. To image the toxin turn-on, Ringe's team used nickel and a mutant that replaced a cysteine that complicated crystallization. When the metal binds, DtxR contorts, its alpha helices coming closer together, which allows the repressor to fit into the major groove of the DNA. At the same time, the amino-terminal ends of the helices unwind, exposing the minor groove. The repressor falls off the toxin gene. Understanding how diphtheria toxin is made may have broader implications. "DtxR is a prototype for the activity of many other virulent bacteria. Most pathogenic bacteria, including those responsible for tetanus, syphilis, tuberculosis, and botulism, have their own versions of this repressor," Ringe concluded after scrutinizing several microbial genomes. New drugs based on the finding would target toxin production. EUROPEAN UNIONS Within 10 days last month, Britain's Zeneca Group PLC merged with Sweden's Astra AB, Germany's Hoechst combined with France's Rhone-Pôulenc, and Sanofi SA and Synthélabo, both of France, joined forces. Call it merger madness, European style. But don't ignore it in the United States, cautions Stelios Papadopoulos, a pharmaceutical industry analyst at Paine Webber Inc. in New York. "I really don't think we should look at them as European events," says Papadopoulos. "This is a global industry." This wave of mergers allows the global drug companies to boost profits by consolidating manufacturing facilities worldwide. For instance, if two European companies have plants in Portugal, one will likely close. Middle management and support positions will also likely suffer. The European mergers will probably result in thousands of job cuts, mostly in manufacturing, support, and middle management. Papadopoulos and other analysts note that job loss is least likely in the R&D side--although those positions aren't completely immune (P. Gwynne, "Merger Mania Produces Positive Signs for R&D," The Scientist, 12 [11]:1, May 25, 1998). "One of the reasons for merging is to invest in R&D," Papadopoulos continues. And one of the reasons for watching the European events is that American-based companies will likely follow suit--for a long time. "This is a trend that will continue for five years," Papadopoulos predicts.

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January 1999

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