Frontlines

Six of Europe's Nobel laureates chastised the European Union's policies on research funding with a letter to all 12 EU leaders demanding action. The six--three winners of the medicine prize in the 1970s and 1980s, two physicists, and a chemist--want funds doubled to stem the flow of talented young scientists from Europe to the United States. "Brain drain--young talented scientists leaving their countries--is making itself felt in most EU countries," the letter warns. The EU has pledged to raise research spending from 2% of gross domestic product to 3% by 2010. But that's not enough, the scientists insist. "Spending plans are inadequate even to put a brake on the process of relative back-sliding of European scientific capability, let alone ... catch up with and overtake the United States." Signatory Sir Aaron Klug, 1982 British chemistry laureate, said it's the way money is allocated, as well as the amounts available, that causes concern. Too much goes into industrial collaborations built on past science, and too little goes to the basic research that drives medical advances. Peter Cotgreave, director of the pressure group Save British Science, agrees: "Often it's not clear if [funding] is used for the best science, or the social engineering projects of the EU. These projects are acceptable but it's not the same as doing world-class science."

New anthrax therapies will be available within two or three years, declares microbiology and molecular genetics professor John Collier. Three treatments developed in his Harvard Medical School lab were found effective on rodents, he told the Congressional Biomedical Research Caucus during a June 19 briefing in Washington, DC. One approach inhibits the binding at the cell surface of an anthrax toxin protein that forms a heptamer complex to deliver two destructive enzymes, edema factor (EF) and lethal factor (LF), into the cytosol via a compartment called the endosome. A second approach uses multiple copies of a peptide to prevent binding of EF and LF to the heptamer. The third strategy incorporates mutant toxin proteins into the heptamer, preventing it from leaving the endosome. Collier revealed encouraging results from a new assay developed by Merck and Co. to screen its library of protease inhibitors for one that will fend off LF, a protease. "Informally, [Merck researchers] told us that they have a very good candidate." He also alluded to several other promising avenues that he was not at liberty to discuss. But, he emphasized that all these drugs would be adjuncts to antibiotics that control bacterial expansion but not the toxin. Prevailing on the caucus to keep funds flowing, Collier decried any suggestion that research should not be published for fear that it might help bioterrorists.

A shortage of PhD scientists who can oversee cell-culture work will intensify a manufacturing crunch that threatens production of protein therapeutics, according to a report in the McKinsey Quarterly (www.mckinseyquarterly.com/article_page.asp?ar=1199&L2=12&L3=62). Revenues from protein-based therapeutics are set to grow at 15% per year until 2007, and monoclonal antibodies drive most of that demand, according to the report "Biopharma's Capacity Crunch," by Ameet Malick, Gary S. Pinkus, and Scott Sheffer. But these antibodies can be produced only in mammalian cell-culture facilities, which are almost fully used. It takes three to five years to build an FDA-approved manufacturing plant. "As that capacity is being built, there is not currently enough manufacturing talent available either from within industry or from newly minted graduates," says Pinkus, a partner in McKinsey's San Francisco office. Enrollment in graduate biochemistry, biomedical engineering, and chemical engineering courses remained at only 26,000 per year from 1992 to 1999. "To find a tissue culture person is difficult to do," adds Ray Cypess, president of the American Type Culture Collection in Manassas, Va. "To find one who is at the cutting edge of the new science is even tougher." Getting good scientists for manufacturing can be a matter of training, says David Nance, CEO of Austin-based Introgen Therapeutics, which manufactures gene-based therapies. "We've recruited people from academic research [who] produce materials and developed a [corporate] culture that allows us to train them in-house." As manufacturing replaces research and discovery as the focus of the biopharmaceutical industry, Pinkus speculates, more scientists will choose manufacturing, and the job will gain in prestige.

Nobel laureate Christiane Nüsslein-Volhard has joined a cadre of Europeans highlighting prejudices against working women in Germany (H. Black, "Toward an equitable Europe, The Scientist 16[10]:59, May 13, 2002). Such intolerance may explain why the proportion of women in professional positions in Germany is among the lowest in Europe. In an essay for the German newspaper Die Zeit (22:36, May 23, 2002), Nüsslein-Volhard, a director of the Max-Planck Institute for Developmental Biology in Tübingen, writes, "The image of women is still that of a mother, wife, lover, or secretary, but rarely that of an equal peer." Currently, there are few role models for women scientists, but "if more women were active in leading positions, others could join more easily," she asserts. According to a 2001 report by the European Commission, women in Germany held only 5.9% of full professor positions in 1998, compared with 18.4% in Finland (1998), 13.2% in Spain (1995-1996) and 13.8% in France (1997-1998). To propel more women into senior positions, Nüsslein-Volhard pleads for fair and objective assessment of women's competence, and support for women who pursue both a career and a family. Women should be able to place their children in nurseries without being viewed as bad mothers, as is often the case in Germany, she asserts.

For those brave scientists willing to publicly share their research failures, a group of editors is launching a Web journal of negative, unexpected results, hoping that such outcomes will advance science even if they do not make headlines. With an online premiere planned in the near future, www.biomedcentral.com, a partner of The Scientist, has been collecting submissions for the Journal of Negative Results in Biomedicine to promote science and medical practice through negative results. "You can learn something when things don't happen as expected," says Bjorn Olsen, the journal's editor in chief. He explains that unpublished work with negative findings often gets repeated, resulting in lost time and money. Olsen plans to feature online articles spanning all disciplines of life sciences and clinical fields that still meet certain guidelines for publication. "We're interested in good science with negative results.... We're not in the business of publishing things that aren't well done." Donald Kennedy, editor in chief of Science, waxes optimistic about Negative Results. "It may help solve the 'file drawer problem' where experiments that don't result positively aren't submitted [because of] fear of rejection.... It could help to prevent false positives." This type of journal has precedent. In 1997, oncology professor Scott Kern, Johns Hopkins University, founded NOGO, the Web journal devoted to negative results in genetic oncology. He seems enthused about Olsen's venture but proffers the warning that many researchers are wary about publishing results that could save time for others. Says Kern, "It usually goes unsaid that you're really only helping the people you're competing with."

A special class of RNA previously identified only in animals has now been found in plants as well, according to a paper in the July 1 issue of Genes and Development (B. J. Reinhart et al., "MicroRNAs in plants," Genes and Development, 16:1616-26, July 1, 2002). MicroRNAs (miRNAs) are short, noncoding RNAs of 20 to 24 nucleotides. To date, miRNAs have been identified in eukaryotic organisms ranging from roundworms, to fruit flies, to mice, to humans. The recent paper is the first to show that plants also possess these tiny regulators of gene expression. The authors describe 16 Arabidopsis miRNAs, eight of which are conserved in the rice genome. "It appears that microRNAs have been shaping gene expression since the last common ancestor of plants and animals," says senior author David Bartel of the Whitehead Institute for Biomedical Research and MIT. MicroRNA function is best understood in Caenorhabditis elegans, where the miRNAs lin-4 and let-7 are known to control the timing of developmental events by inhibiting translation of target messenger RNAs. The precise functions of lin-4 and let-7 and other miRNAs across species remain a subject of ongoing investigation. However, the present study suggests that some miRNAs play important roles in plant development. Mutations in an Arabidopsis homologue of an enzyme called Dicer, which is known to process miRNAs in several species, interfered with the accumulation of molecules. This may explain previously observed developmental abnormalities in these mutant plants.