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case centered on Ashcroft's attempt to sub- poena roughly ... less protested against Ashcroft's access on grounds .... NICHOLAS C. GRASSLY,1 JAY WENGER,2.
COMMENTARY Agent-based models

Colloidal crystals with a difference

Talking to computers

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LETTERS I BOOKS I POLICY FORUM I EDUCATION FORUM I PERSPECTIVES

edited by Jennifer Sills

Speaking Out About U.S. Science Output I WAS AMAZED BY J. MERVIS’S NEWS OF THE WEEK STORY “U.S. OUTPUT FLATTENS, AND NSF wonders why” (3 August, p. 582). Not by the conclusion that U.S. science productivity is flattening out, but because apparently nobody interviewed by the NSF could identify the reason. Had the question been posed of almost any working scientist I know, the simple and accurate answer would have been that the number of papers that are written is diminishing because scientists are able to spend less time writing papers! Instead, we spend ever-more time on the increasingly burdensome administrative requirements of conducting science legally, and on writing, rewriting, and re-rewriting grant applications as the NIH’s pay line drops to catastrophically low levels. As the number of hours in a day is finite and unchanging, something has to give. If I didn’t have to spend the rest of this month ignoring various half-complete manuscripts and rewriting a grant application, I’d be able to explain in more detail. JOHN P. MOORE

CREDIT: IMAGES.COM/CORBIS

Department of Microbiology and Immunology, Weill Medical College, Cornell University, New York, NY 10065, USA.

THE REGULATORY BURDEN THAT ACCELERATED around 1990 is finally affecting the output of U.S. researchers (J. Mervis, “U.S. output flattens, and NSF wonders why,” News of the Week, 3 August, p. 582). Increased funding is reduced by the cost of regulatory compliance: expensive security systems for animals, superfluous accreditation, excessive requirements for cage sterilization, verification of sterility using cultures, and signatures at every step. And, of course, the regulatory documentation takes time away from documenting the research itself. Because of the monumental effort required to gain approval to use animal or human subjects in research, discouraged investigators avoid pursuing experiments that require new approvals, even if the idea may take only a few days to test. The fault lies not with committee members trying to maintain compliance while still permitting research to proceed, but rather with regulations that aim to prevent not only harm, but

the appearance of harm, or even the possibility of harm no matter how unlikely. Even an experiment in which participants must listen to a snippet of song and judge its familiarity is subject to stringent requirements intended to protect those participants from harm. Science is an exploration of the unexpected, and these constraints are suffocating. We must expect creative students to look to other careers when they see how science is done today. They are replaced by those who are comfortable with bureaucracy and who do not know that science used to be accompanied by enthusiasm and spontaneity. The only mystery is why the flat output line has not yet turned down. RICKYE S. HEFFNER Department of Psychology, University of Toledo, Toledo, OH 43606, USA.

THE NEWS OF THE WEEK STORY “ U.S. OUTPUT flattens, and NSF wonders why” by J. Mervis (3 August, p. 582) states that “the total output of U.S. scientists stopped growing in the early 1990s and hasn’t budged since then.” This conclusion is based on publication productivity data from 1992 and 2001. Had more recent data been used, at least one university, Drexel,

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would have shown a 130% increase in publication productivity. Specifically, in 2002 Drexel faculty published 502 articles; in 2006 the number grew to 1165, according to data from Thompson Scientific Web of Science. Drexel’s productivity has not only budged, but surged. The decrease shown in the article for MCP Hahnemann University and Drexel University requires context. For starters, MCP and Drexel are one and the same university. When Drexel acquired the academic units of the bankrupt Allegheny University of the Health Sciences in 1998, it formed an exigent entity called MCP Hahnemann University, which by design was dissolved in 2002 and no longer exists. The compelling reason why Drexel and MCP show a decline in faculty publications during 1992 to 2001 is because of the profound shift in attention, energy, and resources on the part of both faculties as they worked toward the common goal of integrating the nation’s largest private medical school, a college of nursing and health professions, and a school of public health into a consolidated, fully integrated university. This formidable and unprecedented undertaking was a success, and research and publishing are now thriving at Drexel University. Telling a story “by the numbers” alone can sometimes mean a tale half-told. Drexel and likely other universities accept NSF’s challenge to step up productivity and are already meeting it.

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LETTERS

STEPHEN W. DIRECTOR Office of the Provost, Drexel University, Philadelphia, PA 19104, USA.

Threats to Privacy Protection W. W. LOWRANCE AND F. S. COLLINS RAISE excellent points in their Policy Forum “Identifiability in genomic research” (3 August, p. 600). Assuring privacy protections in both genomic research and medicine practice is of urgent concern. A recent Scientific American article (1) describes how even deidentified data can be used to reidentify individuals, specifically when bits of information exist in public databases. The article recounts the work of Lantanya Sweeney, who runs the Data Privacy

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Laboratory at Carnegie Mellon University. Her research found that reidentifying personal information is simpler than one might have imagined. In one case, a banker crossreferenced information in publicly available hospital discharge records against his client list to determine whether any of his clients had cancer. If they did, he called in their loans. In another case, Sweeney found a way to reidentify patients with Huntington disease even after all information about the patients had been deleted from their records. She combined known sequencing data indicating the presence of the disease with hospital discharge records, which included patients’ ages, and succeeded in accurately linking 90% of the Huntington disease patients with DNA records on file. Privacy involves more than the deidentification of personal information, as illustrated by the 2004 U.S. Appeals case Northwestern Memorial Hospital vs. John Ashcroft. The case centered on Ashcroft’s attempt to subpoena roughly 45 Northwestern Memorial Hospital patient records for use in an upcoming trial in the Southern District of New York to challenge the constitutionality of the Partial-Birth Abortion Ban Act of 2003. Although patient records would have been anonymized prior to release, patients nonetheless protested against Ashcroft’s access on grounds that anonymization did not fully protect their privacy. The hospital went to court to block Ashcroft, and the patients prevailed. The court determined that Northwestern

Memorial Hospital was not required to comply with a subpoena from the Justice Department for abortion patients’ medical records. Importantly, the court stated, “Even if there were no possibility that a patient’s identity might be learned from a redacted medical record, there would be an invasion of privacy. If Northwestern Memorial Hospital cannot shield its abortion patients’ records from disclosure in judicial proceedings, moreover, the hospital will lose the confidence of its patients, and persons with sensitive medical conditions may be inclined to turn elsewhere for medical treatment” (2). CAROL ISAACSON BARASH Genetics, Ethics, and Policy Consulting, Inc., Boston, MA 02130, USA. E-mail: [email protected]

References 1. C. Walter, Sci. Am. 297, 92 (July 2007). 2. Northwestern Memorial Hospital vs. John Ashcroft, 362 F.3d 923 (7th Cir. 2004); available at http://fl1.findlaw. com/news.findlaw.com/hdocs/docs/abortion/nwmhash406 04opn.pdf.

Potent Questions About India’s Polio Vaccine IN THEIR REPORT “NEW STRATEGIES FOR THE elimination of polio from India” (17 November 2006, p. 1150), N. Grassly et al. discuss the use of trivalent oral polio vaccine (OPV) in India for supplementary immunizations against type 1 poliovirus. During the past 5 years, OPV efficacy in relation to confirmed

CORRECTIONS AND CLARIFICATIONS News of the Week: “Is battered Arctic Sea ice down for the count?” by R. A. Kerr (5 October, p. 33). The caption for the graphic should have noted more fully that the analysis rendered in the plot was different from the analysis discussed in the text. A particular year’s sea ice area differed in the two analyses, but the long-running downward trend and the sharp decline in 2007 were the same.

TECHNICAL COMMENT ABSTRACTS

COMMENT ON “A G Protein–Coupled Receptor Is a Plasma Membrane Receptor for the Plant Hormone Abscisic Acid” Christopher A. Johnston, Brenda R. Temple, Jin-Gui Chen, Yajun Gao, Etsuko N. Moriyama, Alan M. Jones, David P. Siderovski, Francis S. Willard Liu et al. (Reports, 23 March 2007, p. 1712) reported that the Arabidopsis thaliana gene GCR2 encodes a seven-transmembrane, G protein–coupled receptor for abscisic acid. We argue that GCR2 is not likely to be a transmembrane protein nor a G protein–coupled receptor. Instead, GCR2 is most likely a plant homolog of bacterial lanthionine synthetases. Full text at www.sciencemag.org/cgi/content/full/318/5852/914c

RESPONSE TO COMMENT ON “A G Protein–Coupled Receptor Is a Plasma Membrane Receptor for the Plant Hormone Abscisic Acid” Xigang Liu, Yanling Yue, Wei Li, Ligeng Ma Our study provided experimental evidence that GCR2 is a membrane-associated abscisic acid receptor that interacts with the G protein α subunit GPA1 in Arabidopsis. Although we cannot rule out GCR2 as a lanthionine synthetase homolog, our data indicate that it may define a new type of nonclassical G protein–coupled receptor. Full text at www.sciencemag.org/cgi/content/full/318/5852/914d

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cases of type 1 paralytic poliovirus and number of doses (Grassly et al.’s Fig. 3) suggests that poor-quality vaccine lots are being dispensed during primary and supplementary immunization. The chances of any recipient receiving adequate immunization against three poliovirus serotypes depend on the quality of OPV available locally. Suboptimal immunizing doses or missed immunizations would lead to individuals who do not respond to multiple OPV doses. Assays for the total viral content (1) of the vaccine dose are biased in favor of type 1 poliovirus. Potency assays on tri- or univalent lots retrieved from field usage would be more reliable than any cumulative thermal color changes observed by vaccine vial monitors. Vaccine vial monitors are just physical indicators of temperature. They do not indicate the period (duration) of exposure to such a temperature. Furthermore, they do not indicate the extent of exposure to sunlight and would not indicate the biological activity in the vaccine vial container (2). Inadvertent use of poor immunogenicity lots (3) and brutal handling of OPV aliquots (4) are widespread. It is at least possible that the apparent absence of genetically divergent vaccinederived polioviruses correlates with field usage of poor-quality OPV. SUBHASH C. ARYA AND NIRMALA AGARWAL Sant Parmanand Hospital, 18 Alipore Road, Delhi 110054, India. E-mail: [email protected]

References 1. World Health Organization Manual of laboratory methods for testing of potency of final vaccines used in the WHO Expanded Programme on Immunization (WHO BLG/95.1, Geneva, 1995). 2. VVM for all, Technical Session on Vaccine Vial Monitors (World Health Organization, Geneva, 2002) (downloaded on 23 November 2006 from www.childrensvaccine.org/ files/Getting_started_with_VVMs.pdf). 3. S. A. Omilabu, A. O. Oyefolu, O. O. Ojo, R. A. Audu, Afr. J. Med. Med. Sci. 28, 209 (1999). 4. N. K. Goel, H. M. Swami, S. P. Bhatia, Ind. J. Public Health 48, 200 (2004).

Response ARYA AND AGARWAL ARE CONCERNED ABOUT the potency of trivalent oral polio vaccine (OPV) administered to children in India and the possibility of low potency contributing to low efficacy of this vaccine in Uttar Pradesh. This concern seems to flow from several misunderstandings about the testing, distribution, and use of OPV in India. All OPV released for use in India is tested by the producer and, subsequently, by a national reference laboratory before release. All batches released in India are potent according to international standards. Titers of each individual Sabin virus and a total titer are evaluated. A specific, internationally agreed-

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LETTERS

LETTERS

Letters to the Editor

sion years ago with the trivalent vaccine. Thus, neither of these references supports a serious concern about the cold chain capacity in India as a potential cause for reduced vaccine effectiveness. Finally, the assertion that the absence of genetically divergent vaccine-derived polio virus (VDPV) is consistent with use of poorquality vaccine is not true. The most important risk factor for development of circulating VDPV is low population immunity levels. If the vaccine was poorly immunogenic, low population immunity would result, and one would be likely to see more, not fewer, episodes of circulating VDPV. NICHOLAS C. GRASSLY,1 JAY WENGER,2 R. BRUCE AYLWARD3 1Department

of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London W2 1PG, UK. 2National Polio Surveillance Project, World Health Organization, R. K. Khanna Tennis Stadium, Africa Avenue, Safdarjung Enclave, New Delhi, 110029, India. 3Global Polio Eradication Initiative, World Health Organization, 20 Avenue Appia, CH 1211 Geneva 27, Switzerland.

References 1. National Polio Surveillance Project, data available at www.npsuindia.org. 2. Ministry of Health and Family Welfare, Government of India, New Delhi; data available at www.npsuindia.org.

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Letters (~300 words) discuss material published in Science in the previous 3 months or issues of general interest. They can be submitted through the Web (www.submit2science.org) or by regular mail (1200 New York Ave., NW, Washington, DC 20005, USA). Letters are not acknowledged upon receipt, nor are authors generally consulted before publication. Whether published in full or in part, letters are subject to editing for clarity and space.

(Arya and Agarwal incorrectly state that VVMs do not measure heat exposure over time.) Thus, although the VVM does not directly measure potency, it provides information about the main factor that affects potency. Vaccine vials whose VVMs indicate that they have not been maintained at the correct temperature are discarded. This system ensures that only potent oral polio vaccine is administered to children in India. Monitoring data shows only a very small minority of vaccine vials observed in the field indicate overexposure to heat (less than 1%) (1). In addition, a recent laboratory evaluation of monovalent and trivalent OPV retrieved from the field in Uttar Pradesh during the 2006 mass immunization campaigns demonstrated adequate potency in all vials with VVMs indicating potency [a sample of 345 vials from 69 districts (2)]. Arya and Agarwal cite an article about a Nigerian measles immunization program, which is of negligible relevance to a discussion of the Indian polio immunization program, and an article about the cold chain in Chandigarh, which, although in India, is an area that eliminated wild polio virus transmis-

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upon benchmark titer is used to assess potency (for example, each dose must contain titers of Sabin serotype 1 virus that exceed 106 tissue culture infective doses). Thus, the suggestion that assays used to assess potency are somehow biased and misleading is incorrect. After testing, vaccine is distributed in a refrigerated “cold chain” throughout the country. Each vial of vaccine includes a vaccine vial monitor (VVM), which indicates cumulative heat exposure over time. The VVM is calibrated to alert the vaccinator when the vial has become exposed to enough heat over time to reduce potency to a level that would hinder the protective effect.