Chown, S.L.

Kalwij, J.M.

Procheş, Ş.

Richardson, D.M.

Veldtman, R.

Wilson, J.R.U.

Science

Stellenbosch University SUNScholar Repository

University Investmentin Drug DiscoveryALTHOUGH YOUR SPECIAL SECTION ON DRUGDiscovery (29 July, pp. 721–735) high-lighted important contributions fromacademia, it did not recognize an increas-ingly relevant but underappreciated andunderutilized role for academic researchin drug discovery.Universities invest many millions in basicresearch that exposes disease mechanisms andtherefore unearths new targets. Yet few haveinvested in the relatively modest infrastructurerequired to put their discoveries to the test. Asa result, many promising targets gather dust onthe university shelf. This need not be the case.Developing appropriate assays, screeningmodest-sized compound libraries, using med-ical chemistry to further develop leads, andconducting preliminary tests in animal modelsare functions well suited to academia.Academic researchers often have the bestunderstanding of individual targets, routinelydesign and refine in vitro assays, and haveready access to and experience with the mostappropriate animal models. The pharmaceutical industry (and, to alesser extent, biotech) look at drug discoveryideas emanating from academic research astoo risky and early in development to warrantsignificant investment. This risk aversion is inlarge part a reflection of the economic climateand the changing winds of drug-discoveryreceived wisdom. To bring these ideas to astage where pharma will look at them morecarefully, we can and should advance themthrough at least the first stages of drug discov-ery. Demonstrating a credible mechanism andtarget, proprietary lead compounds, and pre-liminary in vivo efficacy will be enough tobring some of our industry colleagues back tothe table. But this will only happen when aca-demics stop treating drug discovery as theintellectually inferior domain of the commer-cial sector and start seeing it as the naturaldevelopment of their research.ADRIAN J. IVINSONDirector, Harvard Center for Neurodegenerationand Repair, Harvard Medical School, Boston, MA02115, USA. E-mail: adrian_ivinson@hms.harvard.eduA Place at the PharmaTable for Women?THE ARTICLE “IT’S STILL A MAN’SWORLD AT THEtop of big pharma research” (J. Mervis,Special Section on Drug Discovery, News,29 July, p. 724) resonated with me. As a scien-tist in Merck R&D in the 1990s, it was clear tome that women did not have a place at the deci-sion-making table. As years of diversity com-mittees, on-site day care, mentoring programs,coaching, and other HR efforts rolled by, manytalented women figured out that their onlycareer path at Merck R&D was outthe door.Merck, and I suspect manyother “big pharma” companies,are feeling the effects of havingsome of their best talent leavingand taking their brainpower else-where. We have started compa-nies, taken senior positions inbiotechnology firms, and becomeleaders in government and acade-mia. Perhaps this brain drain oftalented women has exacerbatedthe problem of the empty productpipelines of big pharma. The men in charge of R&D tend to pro-mote and recruit other men with whom theyfeel the most comfortable and ignore tal-ented women. Until they are forced by pro-gressive senior executives to include, in sig-nificant numbers, women in their club, theywill not change.LINDA RHODESRhodes & Associates, LLC, 3 White Birch Lane,Holmdel, NJ 07733, USA. E-mail: lrhodes@alcherabio.comCosts and Benefitsof Regulating MercuryMERCURY IS KNOWN TO HAVE DETRIMENTALeffects on human health (1), so it is surpris-ing to read that it may not be worthwhile toregulate mercury releases from U.S. powerplants (“Regulating mercury: what’s atstake?”, T. Gayer, R. W. Hahn, Letters,8 July, p. 244). Although there is legitimatedebate about the cost of implementationand the choice of emission reductionapproach, we feel that the estimated bene-fits of emission reduction of $100 millionaccrued over 15 years have been grosslyunderstated by Gayer and Hahn. Their proposed benefit was based on astudy of willingness-to-pay for chelationtherapy to reduce lead in children. However,lowering levels of lead by chelation has notbeen demonstrated to improve cognition(2). Similarly, although chelation therapymay remove methyl- and ethylmercury, itcannot reverse central nervous system dam-age (3), implying that prenatal mercuryexposure leads to lifelong lost benefits,irrespective of money spent on removingthe causal agent from the body after thedamage has been done. Thus, an approach based on lifelong lossesin income better estimates the benefits ofreducing mercury emissions (4). This approachattributes subsequent losses in lifelong earn-ings as a result of lower IQ to the loss in a child’sIQ from prenatal methylmercury exposure.The estimated lifelong losses in income for allU.S. children affected in the year 2000 was$1.3 billion per year (range: $0.1 to $6.5billion), which would lead to a $15.9-billionloss in income (range: $1.2 to $79.9 billion,discounted at a rate of 3% per annum) overthe 15-year period considered by Gayer andHahn. Therefore, by only considering theloss of earnings due to exposure to mercurygenerated by U.S. power plants, loweringprenatal exposure by reducing emissionsmay have considerable economic benefits,likely exceeding the estimated costs of $4billion to $19 billion. DIRK ZELLER AND SHAWN BOOTHFisheries Centre, University of British Columbia,Vancouver, BC V6T 1Z4, Canada. E-mail:d.zeller@fisheries.ubc.caReferences1. P. Grandjean et al., Neurotoxicol. Teratol. 19, 417(1997).2. K. N. Dietrich et al., Pediatrics 114, 19 (2004).3. X. Liu et al., Pediatrics 110, 787 (2002).4. L. Trasande, P. J. Landrigan, C. Schechter, Environ.Health Perspect. 113, 590 (2005).Response IN OUR STUDY, WE ESTIMATED THE COSTSand benef its of the U.S. EnvironmentalProtection Agency’s (EPA) power plant mer-cury regulation. To estimate the benefits ofmercury reduction, we considered each linkin the pathway, including the reduction ofemissions from U.S. power plants; reduc-tions in mercury deposition; reductions ofmethylmercury in U.S. freshwater andmarine fish; reductions of methylmercuryconsumption from U.S. fish by U.S. resi-LETTERS777Universities invest manymillions in basic research thatexposes disease mechanisms…[y]et few have invested in therelatively modest infrastructurerequired to put theirdiscoveries to the test.”–IVINSON“www.sciencemag.org SCIENCE VOL 310 4 NOVEMBER 2005Published by AAASL E T T E R Sdents; reductions of methylmercury in U.S.women of childbearing age; and IQimprovements in U.S. children. For eachlink, we used the best available evidenceand, if anything, tended to err on the side ofoverstating benefits. Only at the end did wemonetize estimates of IQ improvements,based on a study of parental willingness topay for IQ increases through chelation.Zeller and Booth contend that our esti-mate of the benefits of mercury reduction is“grossly understated” based on their claimthat our estimate of the value of an IQ pointis flawed. They cite a study by Trasandeet al. (1) claiming that benefits of mercuryreduction are $1.3 billion per year. Un-fortunately, they are comparing apples withoranges. The $1.3 billion estimate (1) is forthe benefits of eliminating all U.S. powerplant mercury emissions. Zeller and Boothapply this annual measure of complete elim-ination of power plant mercury emissions toeach year from 2005 to 2020. It is incorrectto compare the costs of EPA’s regulation thateliminates a fraction of the power plantemissions to the benefits of eliminating allpower plant emissions of mercury (whichwould cost considerably more to achieve). Zeller and Booth suggest that the mone-tized benefits we use for IQ may be under-stated. We agree that the willingness-to-pay numbers for IQ may understate thebenefits of IQ. The value of an IQ pointsuggested by Trasande et al. (1) is about anorder of magnitude greater than ourestimate. However, as we noted in ourLet ter, using their estimate does notchange our finding that the costs of the reg-ulation are likely to exceed benefits. Zeller and Booth’s claim of mercury’sdetrimental effects might be overstated.They cite Grandjean et al.’s study (2) of theFaroe Islands to support their claim that thedetrimental effects of mercury are “known.”They do not mention a study of theSeychelles (3) that did not find evidence ofsuch a link and a study in New Zealand (4)that found mixed evidence. Even Grandjeanet al. (2) found mixed results for the relation-ship between mercury and IQ scores.Nonetheless, we used conservative estimatesof the IQ-mercury relationship even whenthey are not statistically different from zero. We think that policy-makers shoulddesign regulations for controlling mercuryemissions so that expected benefits exceedexpected costs. The current approach failsthat test.TED GAYER1 AND ROBERTW.HAHN21Public Policy Institute, Georgetown University,3520 Prospect Street, NW,Washington, DC 20007,USA. 2American Enterprise Institute–BrookingsJoint Center, 1150 17th Street, NW, Washington,DC 20036, USA.References1. L. Trasande, P. J. Landrigan, C. Schechter, Environ.Health Perspect. 113, 590 (2005).2. P. Grandjean et al., Neurotoxicol. Teratol. 19, 417(1997).3. G. J. Myers et al., Lancet 361, 1686 (2003).4. T. Kjellstrom et al., Physical and Mental Developmentof Children with Prenatal Exposure to Mercury fromFish. Stage 2: Interviews and Psychological Tests atAge 6 (National Swedish Environmental Board, Solna,Sweden, 1989).Landscape Corridors:Possible Dangers?THE REPORT “EFFECTS OF LANDSCAPE CORRI-dors on seed dispersal by birds” (1 July,p. 146) by D. J. Levey et al. shows that land-scape corridors increase the movement ofbirds between patches of habitat in a frag-mented landscape, and that this facilitatesthe movement of bird-dispersed seeds.Another study, in the same experimentalsetting, found that corridors increase inter-patch insect pollination (1). Both studiesconclude by emphasizing the conservationvalue of habitat corridors. However, land-scape corridors also facilitate the spread ofPublished by AAASinvasive alien species (2). Although thepotential negative effects of habitat connec-tivity were stated almost two decades ago (3),these seem to have been largely ignored in theevaluation of corridors as a conservation tool.Alien plants with attractive flowers andfruit can hijack generalist pollinators andseed dispersers from indigenous plantspecies (4). By increasing alien propagulepressure, invasive species outcompete andreplace local biota (5). Indeed, the spread ofinvaders is often facilitated by corridors,either natural (rivers, coastlines, ridges) orman-made (roads and railways). In this con-text, it is worth mentioning that all theplants considered in the South Carolinastudies [Levey et al.; (1)] are aliens ofconcern in parts of the world [Lantanacamara (6), Rudbeckia hirta (7), Morella(=Myrica) cerifera (8)]. Moreover, theEastern Bluebird (Sialia sialis) thatdispersed Morella seeds is also known todisperse seeds of the alien tree Sapiumsebiferum in the eastern United States (9).Presently, land managers are advised tobuild habitat corridors to reduce the effects ofhabitat fragmentation, but habitat barriers arealso built to manage the spread of invasivespecies (10). It is ironic that habitat corridorsdo not always link the seemingly separatefields of conservation and invasion biology.Both habitat fragmentation and invasivespecies have resulted in the loss of large sec-tions of biodiversity, and their combinedimpacts must be better understood. The mod-eling tools developed in the present studypresent a useful opportunity for developing amore integrated approach to the evaluation ofcorridors as a conservation management tool.ERBAN PROCHE , JOHN R.U.WILSON,RUANVELDTMAN, JESSEM.KALWIJ,DAVIDM.RICHARDSON, STEVEN L. CHOWNCentre for Invasion Biology, Department ofZoology and Botany and Department ofConservation Ecology, University of Stellenbosch,Matieland 7602, South Africa.References1. P.A.Townsend, D. J. Levey, Ecology 86, 466 (2005).2. D.A. Saunders, R. J. Hobbs, Eds., Nature Conservation 2:The Role of Corridors (Surrey Beatty & Sons, ChippingNorton,Australia, 1991).3. D. Simberloff, Annu. Rev. Ecol. Syst. 19, 473 (1988).4. D. M. Richardson, N. Allsopp, C. M. D’Antonio, S. J.Milton, M. Rejmánek, Biol. Rev. 75, 65 (2000).5. J. L. Lockwood, P. Cassey, T. Blackburn, Trends Ecol.Evol. 20, 223 (2005).6. See www.gisp.org.7. J. S. Meidell, H. L. Oppenheimer, R. T. Bartlett, BishopMus. Occ. Pap. 49, 17 (1997).8. E. U. Zajac, Monogr. Bot. 40, 1 (1974).9. I. J. Renne, W. C. Barrow, L. A. J. Randall, W. C. Bridges,Div. Distrib. 8, 285 (2002).10. K.A.With, Conserv. Biol. 16, 1192 (2002).ResponsePROCHE ET AL. POINT OUT THAT CORRIDORSmay increase the spread of exotic species. Weagree that the function of corridors is blind tothe geographic origin of species that use them.L E T T E R SNeuroscienceADVERTISER DIRECTORYTurn to page 875Advances in:The following organizations have placed ads in theSpecial Advertising SectionADVERTISER PageCarl Zeiss ..................................877Nikon ...........................................874The Challengeof NeurologicalDiseasePublished by AAASL E T T E R Swww.sciencemag.org SCIENCE VOL 310 4 NOVEMBER 2005 783The issue before conservation biologists andland managers, however, is not whether corri-dors are without costs, but whether they pro-vide a net benefit in the maintenance of naturalcommunities. In this context, it is important tokeep in mind that the benefits of habitat corri-dors to native species have been clearlydemonstrated, whereas their impact on thespread of exotic species is largely conjectural. Rather than debating the potential draw-backs of corridors, scientists should focusattention on understanding how corridorsfunction and which types of species aremost likely to benefit from them. For exam-ple, because invasive species are excellentdispersers (by definition), corridors maynot further increase their successful colo-nization of new habitat patches. On theother hand, many native species of conser-vation concern have limited dispersal abili-ties and therefore would be more likely tobenefit from corridors. Understanding corridors at a mechanisticlevel will better enable us to extrapolate theireffects from well-studied species and smallspatial scales to less-known species and land-scape scales; our paper aimed toward this goal.DOUGLAS J. LEVEY,1 BENJAMIN M. BOLKER,1JOSHUA J.TEWKSBURY,1* SARAH SARGENT,2NICK M. HADDAD31Department of Zoology, University of Florida, PostOffice Box 118525, Gainesville, FL 32611–8525,USA. 2Department of Biology, Allegheny College,Meadville, PA 16335, USA. 3Department ofZoology, North Carolina State University, Raleigh,NC 27695–7617, USA.*Current Address: Department of Biology, Box351800, University of Washington, Seattle, WA98195–1800, USA.TECHNICAL COMMENT ABSTRACTSCOMMENT ON “A Brief History of Seed Size”Peter J. Grubb, David A. Coomes, Daniel J. MetcalfeMoles et al. (Reports, 28 Jan. 2005, p. 576) suggested that larger plants have larger seeds because larger offspringoffset the lower survivorship to adulthood inherent in longer juvenile periods.However,that view is not consistentwith the wedge-shaped relationship between log seed size and log plant height. Most importantly, the range offeasible seed sizes increases dramatically with whole-plant size.Full text at www.sciencemag.org/cgi/content/full/310/5749/783aRESPONSE TO COMMENT ON “A Brief History of Seed Size”Angela T. Moles, David D.Ackerly, Campbell O.Webb, John C.Tweddle, John B. Dickie, MarkWestobyMechanical constraints might prevent small plants from making very large seeds. However, data for 2589 speciesreveal an absence of large plants that make very small seeds.This cannot be explained by mechanical constraint.Coordination of life history traits provides a more plausible explanation for the overall shape of the relationshipbetween seed mass and plant size.Full text at www.sciencemag.org/cgi/content/full/310/5749/783bLetters to the EditorLetters (~300 words) discuss material publishedin Science in the previous 6 months or issues ofgeneral interest. They can be submittedthrough the Web (www.submit2science.org) orby regular mail (1200 New York Ave., NW,Washington, DC 20005, USA). Letters are notacknowledged upon receipt, nor are authorsgenerally consulted before publication.Whether published in full or in part, letters aresubject to editing for clarity and space.Published by AAAS

Landscape corridors: Possible dangers?

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Landscape corridors: Possible dangers?

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