Nonprofit Research Institute Research Articles

Nonprofit model for drug discovery and development

AbstractSRI International, a nonendowed, nonprofit research institution, has developed a successful model for drug discovery and development using funding from a variety of sources. We have vertically integrated basic and applied research, drug discovery, and preclinical drug development expertise and capabilities. Funding sources include state and federal government grants and contracts, and our unique model allows us to translate our discoveries into clinical‐ready drug candidates. Drug Dev Res 68:186–196, 2007. © 2007 Wiley‐Liss, Inc.

Phylogenetic reconstruction from non-genomic data

Recent results related to horizontal gene transfer suggest that phylogenetic reconstruction cannot be determined conclusively from sequence data, resulting in a shift from approaches based on polymorphism information in DNA or protein sequence to studies aimed at understanding the evolution of complete biological processes. The increasing amount of available information on metabolic pathways for several species makes it of greater relevance to understand the similarities and differences among such pathways. These similarities can then be used to infer phylogenetic trees not based exclusively in sequence data, therefore avoiding the previously mentioned problems. In this article, we present a method to assess the structural similarity of metabolic pathways for several organisms. Our algorithms work by using one of the three possible enzyme similarity measures (hierarchical, information content, gene ontology), and one of the two clustering methods (neighbor-joining, unweighted pair group method with arithmetic mean), to produce a phylogenetic tree both in Newick and graphic format. The web server implementing our algorithms is optimized to answer queries in linear time. The software is available for free public use on a web server, at the address http://www.jaist.ac.jp/~clemente/cgi-bin/phylo.pl. It is available on demand in source code form for research use to educational institutions, non-profit research institutes, government research laboratories and individuals, for non-exclusive use, without the right of the licensee to further redistribute the source code.

Guest Editorial: Global Perspective on Environmental Health

Guest Editorial: Global Perspective on Environmental Health

Salty taste acceptance by infants and young children is related to birth weight: longitudinal analysis of infants within the normal birth weight range

Birth weight and sodium intake are both associated with risk for hypertension. It is not known whether birth weight influences response to salty taste. To assess the relationship between birth weight and salty taste acceptance of infants and young children. Acceptance of salty taste was assessed at 2 (n = 80) and 6 (n = 76) months in infants (birth weight >2.5 kg) enrolled in a prospective cohort study. Acceptance was expressed as proportional intake following 1-min ingestion tests with water and salt solutions (0.17 and 0.34 mol/l NaCl, in water). Birth weight was obtained by maternal report. Questionnaires completed by mothers and food-ranking procedures performed by children evaluated salt liking and preference in a subset (n = 38) of subjects at preschool age (36 or 48 months). Nonprofit basic research institute in Philadelphia, PA, USA. Regression analysis revealed significant negative associations between birth weight and acceptance of salty taste at 2 months (0.17 mol/l, P < 0.0001; 0.34 mol/l, P < 0.01) but not at 6 months. Relationships were not affected by adjustment for potential confounders. In preschoolers, greater liking of (P < 0.05) and preference for (P < 0.01) salty foods was associated with lower birth weight in simple, but not adjusted, models. Measures related to salty taste preference were inversely related to birth weight over the first 4 years of life. Additional studies should substantiate these findings and explore whether early response to salty taste predicts future sodium intake, blood pressure, or other public health-related outcomes. National Institutes of Health (DC 00882).

General News

Increasing Obesity Concerns in Australia. Non-profit Tropical Disease Research Institute in Singapore. Challenges in Thailand Biotech Industries.

A Response to Drs. Hazlett, Havenner and Bazelon

In July 2003, the Phoenix Center released POLICY BULLETIN NO. 5, Competition and Bell Company Investment in Telecommunications Plant: The Effects of UNE-P (July 2003) that evaluated, using a simple economic and econometric model, the short-run relationship between UNE-P and Bell Company investment in telecommunications plant at the state level. For the analysis, data from the Automated Reporting and Management Information System (ARMIS) and other publicly-available data were used. From the results of this econometric analysis, we concluded that UNE-P had a positive and sizeable effect on BOC investment in telecommunications plant, with each UNE-P line increasing on average BOC net investment by about $759.00. Subsequently, two formal responses to the analysis set forth in POLICY BULLETIN NO. 5 were released. On one hand, in a document filed in Verizon's Forbearance Petition (WC Docket No. 03-157), Verizon employed Drs. Thomas Hazlett (the Manhattan Institute), Arthur Havenner (Univ. California - Davis), and Coleman Bazelon (Analysis Group) to comment on the empirical analysis contained in the BULLETIN. Verizon's advocates proposed several modifications to our model, and presented a few alternate specifications. On the other hand, Z-Tel Communications, Inc. asked Dr. Carter Hill (Louisiana State University) to review the declaration of Hazlett, Havenner, and Bazelon as well as provide comments on the econometric model in POLICY BULLETIN NO. 5. Although the Phoenix Center, as a non-profit research institution under Section 501(c)(3) of the U.S. Internal Revenue Code, does not seek to influence the political process by participating as a party in any regulatory proceeding or engaging in lobbying of legislatures, we nonetheless believed it appropriate to respond to the comments of Hazlett, Havenner and Bazelon (HHB I) and to Carter Hill (Hill) in the interest of academic debate. This response was issued as POLICY BULLETIN No. 6, UNE-P Drives Bell Investment: A Synthesis Model (September 2003), where we summarized an extensive effort to evaluate the robustness of the empirical results reported in POLICY BULLETIN NO. 5. While these new specifications represented a synthesis of the modeling preferences of the Phoenix Center and the aforementioned economists, they nonetheless remained true to the neoclassical model of investment and valid econometric practice, to the extent allowed by the data. Despite wide variations in model specification, all our new empirical models confirmed that UNE-P competition a positive relationship between Bell Company investment in local telecommunications plant. As such, our new models affirmed both the results and specification of the empirical models in POLICY BULLETIN NO. 5. Notwithstanding, Verizon again hired Drs. Hazlett, Havenner and Bazelon to file a formal critique of POLICY BULLETIN No. 6 as part of Verizon's comments to the FCC's pending TELRIC proceeding. Again, although the Phoenix Center as a non-profit research institution under Section 501(c)(3) of the U.S. Internal Revenue Code does not seek to influence the political process by participating as a party in any regulatory proceeding or engaging in lobbying of legislatures, we nonetheless believe it appropriate to consider formally the comments of Hazlett, Havenner and Bazelon (now HHB II) as there is always the possibility that critical review, even when adversarial rather than academic in nature, may prove useful in improving our analyses or, in some cases, reveal trivial or substantial flaws that we may have inadvertently committed or overlooked. Moreover, such comments are also useful in providing direction for future research. After review, we believe the additional efforts by Verizon advocates Drs. Thomas Hazlett, Art Havenner, and Coleman Bazelon to discredit the statistical analysis summarized in POLICY BULLETIN NOS. 5 and 6 to be uncompelling. The nature of HHB's criticisms frequently relate to what cannot be estimated (given limited data), rather than what we have or can estimate. Much of their criticism is also directed at a statistical problem for which our models did not suffer (i.e., heteroscedasticity). This line of attack is unpersuasive and, in many cases, irrelevant. As such, we find no reason to alter or change our analysis or interpretation of it as summarized in the POLICY BULLETINS. We leave it to the discerning public, armed with the POLICY BULLETINS and all relevant documents (all made freely available at the Phoenix Center website), to make an educated decision on the validity of the analysis and the criticisms of it. As always, we appreciate the attention (adversarial or not), which signifies the relevance of our work.

Designing and executing scientific workflows with a programmable integrator

As in many other fields of science, computational methods in molecular biology need to intersperse information access and algorithm execution in a computational workflow. Users often find difficulties when transferring data between data sources and applications. In most cases there is no standard solution for workflow design and execution and tailored scripting mechanisms are implemented in a case by case basis. In this paper, we present a general purpose 'programmable integrator' that can access information from a variety of sources in a coordinated manner. Its usefulness in complex bioinformatics applications is claimed and supported by some application examples. Tools are freely available to non-profit educations and research institutions. Usage by commercial organizations requires a license agreement. Software requirements: Java v1.3 (http://java.sun.com), Xerces XML Parser (http://xml.apache.org/xerces-j) and Kweelt implementation of XQuery (http://kweelt.sourceforge.net/).

Bridging The Gap In California

Five California research institutions have formed a consortium aimed at moving potential drugs out of the state's laboratories and into the arms of the pharmaceutical industry. PharmaSTART—for BioPharmaceutical Support for Translating & Advancing Research & Technology—is led by SRI International, a nonprofit research institute, and includes Stanford University, the University of California campuses in San Diego and San Francisco, and the UCSF campus of the California Institute for Quantitative Biomedical Research. Glenn Rice, vice president of SRI's Biosciences Division, explains that California's universities, research institutes, and smal companies are developing promising drugs, but many of them can't bridge the gap to the marketplace because they are seen as risky investments by venture capitalists and big pharmaceutical companies. At the same time, he says, the drugs' developers aren't equipped to perform the FDA-compliant tasks required to start clinical trials on their own. PharmaSTART seeks to mak...

A COLLABORATIVE TRIUMVIRATE

HARVARD UNIVERSITY, THE Massachusetts Institute of Technology, and the Whitehead Institute for Biomedical Research, a nonprofit research and educational institution affiliated with MIT, have announced a unique collaboration: the formation of a joint institute specializing in genomics, chemistry and biomedicine. The Eli & Edythe L. Broad Institute will combine MIT and Whitehead strengths in human genome sequencing and analysis, comparative genomics, and bioengineering with Harvard expertise in chemical genomics and biomedicine. Researchers and administrators at the three institutions had batted around the idea of a joint institute for a couple of years. For much of that time, the possibility that the concept would actually come to fruition seemed remote, given the slim history of major collaboration between the Harvard and MIT camps. What got the plan moving off the drawing boards—and into the press conference last Thursday in Cambridge, Mass., at which the institute was announced—was a $100 million grant ...

Motu, Excellence in Economic Research and the Challenges of 'Human Dimensions' Research

Economics as a 'trade' does very well in New Zealand. Economists are taken relatively seriously in government policy processes. For better or worse, economic ideas were major drivers of the reforms in the late 1980s and early 1990s. Plenty of well-paid job opportunities exist in the private sector and in government. Large numbers of economics undergraduates mean that economics departments in Universities are not under threat. Economics as a science doesn't necessarily do so well. This article discusses some of the opportunities and challenges ahead in creating a vibrant economic research community in New Zealand that can usefully contribute to public policy. We bring particular attention to the challenges of producing good interdisciplinary work. Nearly all policy problems are multifaceted and cannot be understood using insights from one discipline alone. Motu is a non-profit research institute that has been set up specifically to address these challenges. At the end of the article we outline our vision of how we are becoming part of the solution and give some suggestions for how the government and researchers could facilitate our and others' efforts.

Automated Meteorological Reports from Commercial Aircraft

Commercial aircraft now provide over 130,000 meteorological observations per day, including temperature, winds, and in some cases, humidity, vertical wind gust, or eddy dissipation rate (turbulence). The temperature and wind data are used in most operational numerical weather prediction models at NCEP and at other centers worldwide. At nonsynoptic times, these data are often the primary source of upper-air information over the United States. Even at synoptic times, these data are critical in depicting the atmosphere along oceanic air routes. A Web site [http://acweb.fsl.noaa.gov/] has been developed that gives selected users access to these data. Because the data are proprietary to the airlines, real-time access is restricted to entities such as government agencies and nonprofit research institutions (although sample past data are available to all). Data can be displayed in a variety of ways and can be downloaded for local processing. These data are described here, and examples of how they have been usefu...

Danish chiropractic patients then and now—a comparison between 1962 and 1999

Background: Little is known about changes in the chiropractic patient population over time. Objective: To compare 2 surveys describing the Danish chiropractic patient population. Design: Data concerning location of primary complaint and its duration for patients in Danish chiropractic offices between 1962 and 1999 were compared. Setting: Private chiropractic practice and nonprofit research institution. Outcome Measures: Location of primary diagnosis/complaint, duration of complaint. Results: In 1962, data for 1118 patients were collected, with a participation rate of 93%. In 1999, data for 1897 patients were collected. Of all Danish chiropractic clinics, 88% participated in the study, and 94% of all eligible patients filled out a questionnaire. In both 1962 and 1999, the most frequent complaints were pain in the lower back or neck either alone or with radiation to the extremities (roughly 70% of patients). In 1962, almost 4 times as many patients complained of headache as in 1999 (11% vs 4%). Although there were significant differences, less that 10% of patients presented with a nonmusculoskeletal disorder in both 1962 and 1999 (7% vs 3%). In 1962, almost half of the patients had had their complaint for more than 1 year; in 1999, approximately 80% of patients had had their complaint for less than 1 year. Conclusions: In both 1962 and 1999, Danish chiropractors primarily treated patients with pain syndromes related to the lower back and neck. Patients presenting with type O disorders comprised less than 10% of the total patient population in both surveys. (J Manipulative Physiol Ther 2003;26:65-9)

Affymetrix, Inc.

Affymetrix creates breakthrough tools for applications in the drug development process and pharmacogenomics. By applying the principles of semiconductor technology to the life sciences, Affymetrix has created the GeneChipmicroarray platform for both gene expression analysis (mRNA) and genetic analysis (DNA). The company's integrated system is setting the standard for basic research and target identification and is now being adopted in additional research applications, such as target validation and toxicogenomics, as well as in healthcare applications including clinical trials and health management. Affymetrix' current customers include pharmaceutical, biotechnology, agrochemical, diagnostic and consumer product companies as well as academic, government and other non-profit research institutions. Additional information on Affymetrix can be found at www.affymetrix.com.

Building Regional Innovation Capacity

San Diego, California is now one of the most innovative regions in the USA. In the past fifteen years it has transformed itself from an economy dominated by defence contracts, tourism and real estate into a major centre for academic research and high-tech industry This article examines the various means by which this transformation has been achieved and suggests that the experience of San Diego offers guiding principles for developing innovative capacity in regions elsewhere in the USA and in other countries. The paper concentrates on the three major ‘hooks’ that the authors identify as critical to successful, regional development: (a) the store of intellectual capital in the region; (b) the character and extent of catalytic business and financial networks; and (c) the breadth and depth of the advanced skills and knowledge of the human capital. With specific reference to San Diego's biotechnology and telecommunications clusters, the authors demonstrate how non-profit research institutions have created powerful research clusters in the region and how these clusters, in partnership with technology-focused networks of business and professional leadership, have provided those three essential ingredients. While certain elements of the San Diego story are attributable to the specific history and assets of the region, the key factors that have shaped its growth suggest principles of economic transformation that are applicable throughout the world.

Reviving Biomedicine: New Basel institute tackles aging and aims to bolster Swiss research (Research funding)

The Alps have protected the Swiss from centuries of invaders, but even the towering mountains can't shield them from aging. Over the next 50 years, the number of people in industrialized nations aged 65 and over is expected to double, and Switzerland is no exception. Although the snowy passes won't keep away old age, a new Swiss institute aims to take on the scientific and societal challenges associated with the demographic change. On 29 November 2001, Gian-Reto Plattner, vice rector of the University of Basel, announced the formation of the Basel Institute for Diseases of Aging (BIDA), which will dedicate itself to investigating the biology of growing old. The institute was conceived in December 2000, when a group of biochemistry and medical researchers from the Novartis Research Foundation's Friedrich Miescher Institute in Basel phoned the vice rector. They wanted to "do something," he says, to focus the considerable science and technology expertise in Basel and the surrounding region, which has been feeling the impact of a spate of negative developments, including last year's closing of the Basel Institute for Immunology and a pronounced exodus of scientists. A brainstorming session led to the idea of a center of excellence in biomedical research. The group hoped to combine the region's strengths--a university, teaching hospitals, and biotechnology and pharmaceutical companies--to address a topic that is "scientifically novel and interesting and [that] at the same time somehow touches society's interest in a strong way," says Plattner. Aging topped the list of potential areas of study, and BIDA was born. BIDA will operate as an independent, nonprofit research institution associated with the University of Basel. In addition, BIDA will partner with the rest of the biomedical research community in the area to develop a comprehensive science and technology network that will strengthen research and promote economic growth. This group will coordinate resources such as tissue banks, bioinformatics services, facilities for studying animals that model human diseases, and molecular and cellular imaging systems--and negotiate arrangements for their shared use. Rather than study geriatric diseases per se, BIDA will focus on the conditions that predispose people to these disorders, many of which begin well before old age takes hold. The institute's research will home in on degenerative processes, for example, such as cancer metastasis and the neurodegeneration of Alzheimer's disease. The full-grown BIDA will comprise about 20 to 25 research groups totaling roughly 300 researchers. Local government, the University of Basel, and the Novartis Research Foundation provided seed money for a feasibility study and a planning phase. The institute itself will require an additional initial investment of approximately 100 million Swiss francs (US$61.2 million) for building and equipment, plus yearly operating costs of about 40 million Swiss francs (US$24.5 million). The target date for completion of the institute is roughly 2008. But if all goes well, the institute will begin to operate in 2003 on rented premises, says Plattner. BIDA has assembled a star-studded council to hit up public and private sources for the money still required to launch the project. The council includes Nobel laureates, the former head of the Union Bank of Switzerland, and other leaders from government, science, and industry. "We will try to be a little bit American in the way it's done," says Plattner, referring to optimism, enthusiasm, and willingness to go after private money. "Whether that works with Swiss people, we have to find out." --Giselle Weiss Further Reading • Swiss National Science Foundation http://www.snf.ch/default_en.asp • Friedrich Miescher Institute http://www.fmi.ch • Biozentrum at the University of Basel http://www.biozentrum.unibas.ch

A Comparison of U.S. and European University-Industry Relations in the Life Sciences

We draw on diverse data sets to compare the institutional organization of upstream life science research across the United States and Europe. Understanding cross-national differences in the organization of innovative labor in the life sciences requires attention to the structure and evolution of biomedical networks involving public research organizations (universities, government laboratories, nonprofit research institutes, and research hospitals), science-based biotechnology firms, and multinational pharmaceutical corporations. We use network visualization methods and correspondence analyses to demonstrate that innovative research in biomedicine has its origins in regional clusters in the United States and in European nations. But the scientific and organizational composition of these regions varies in consequential ways. In the United States, public research organizations and small firms conduct R&amp;D across multiple therapeutic areas and stages of the development process. Ties within and across these regions link small firms and diverse public institutions, contributing to the development of a robust national network. In contrast, the European story is one of regional specialization with a less diverse group of public research organizations working in a smaller number of therapeutic areas. European institutes develop local connections to small firms working on similar scientific problems, while cross-national linkages of European regional clusters typically involve large pharmaceutical corporations. We show that the roles of large and small firms differ in the United States and Europe, arguing that the greater heterogeneity of the U.S. system is based on much closer integration of basic science and clinical development.

Extending traditional query-based integration approaches for functional characterization of post-genomic data.

To identify and characterize regions of functional interest in genomic sequence requires full, flexible query access to an integrated, up-to-date view of all related information, irrespective of where it is stored (within an organization or across the Internet) and its format (traditional database, flat file, web site, results of runtime analysis). Wide-ranging multi-source queries often return unmanageably large result sets, requiring non-traditional approaches to exclude extraneous data. Target Informatics Net (TINet) is a readily extensible data integration system developed at GlaxoSmith- Kline (GSK), based on the Object-Protocol Model (OPM) multidatabase middleware system of Gene Logic Inc. Data sources currently integrated include: the Mouse Genome Database (MGD) and Gene Expression Database (GXD), GenBank, SwissProt, PubMed, GeneCards, the results of runtime BLAST and PROSITE searches, and GSK proprietary relational databases. Special-purpose class methods used to filter and augment query results include regular expression pattern-matching over BLAST HSP alignments and retrieving partial sequences derived from primary structure annotations. All data sources and methods are accessible through an SQL-like query language or a GUI, so that when new investigations arise no additional programming beyond query specification is required. The power and flexibility of this approach are illustrated in such integrated queries as: (1) 'find homologs in genomic sequence to all novel genes cloned and reported in the scientific literature within the past three months that are linked to the MeSH term 'neoplasms"; (2) 'using a neuropeptide precursor query sequence, return only HSPs where the target genomic sequences conserve the G[KR][KR] motif at the appropriate points in the HSP alignment'; and (3) 'of the human genomic sequences annotated with exon boundaries in GenBank, return only those with valid putative donor/acceptor sites and start/stop codons'.

Universities Have Toed The Line On Cost Sharing

Increasing pressure on universities to pay more of the indirect costs of doing research—costs that have held steady for the past decade—would be detrimental to the research enterprise, according to an analysis of university cost sharing on federal grants released last week by the White House Office of Science & Technology Policy (OSTP). The analysis of facilities and administrative (F&A) costs—also known as indirect costs—further indicates that increasing the share of costs borne by universities could force administrators to reduce spending for research and education or to raise tuition. The analysis was conducted by OSTP and RAND, a nonprofit research institution based in Santa Monica, Calif. By wording and implication, the report is clearly meant to stave off possible congressionally mandated reductions in indirect cost funds that accompany research grants to academic investigators. In the past, the cost-sharing issue has brought controversy and scandal to the university research community. A lack of ...

CHEMISTRY ENLISTED TO TREAT DRUG ABUSE

From the ACS meeting For some time, scientists have been trying to bring chemistry to bear on the problems of substance abuse and drug addiction. In a Division of Medicinal Chemistry session on addiction at the American Chemical Society national meeting in New Orleans last month, researchers from academia and a nonprofit research institute reported that a number of such efforts are beginning to come to fruition. Three speakers described medicines that are poised to move into the drug development pipeline: monoclonal antibodies that represent the first potential long-term treatment for phencyclidine (PCP) abuse; two immunological therapies to blunt the effects of cocaine abuse—an addiction for which there is currently no effective drug-based therapy; and 3-phenyltropane compounds being developed as cocaine abuse medications. A fourth presenter reported progress toward a better understanding of the neurochemistry of alcohol abuse—research that could lead to the development of new alcoholism treatments. In t...

The economic impact of biomedical research: a case study of voluntary institutions in the New York metropolitan region.

This study estimates the economic significance of biomedical research for a geographic region. Through a survey of nonprofit biomedical research institutions in the metropolitan New York region and an analysis of research budget data obtained from the area's six largest research institutions, estimates were made of the spending effect of biomedical research on the region. Biomedical research undertaken by the voluntary institutions in metropolitan New York accounted for almost $1.15 billion per year in direct spending in 1991. When the indirect and induced ripple effects of this spending on the regional economy were considered, the total annual spending impact was over $2.3 billion. Sponsored biomedical research directly generated 19,816 jobs per year in the host institutions. The indirect and induced job creation in the region amounted to an additional 12,773 jobs per year for a total of almost 32,600 regional jobs per year. As economic development becomes more competitive locally, regionally, and internationally, the biomedical sciences that have always been intrinsically valued gain extrinsic value. Therefore, techniques for estimating their economic impact are becoming increasingly important.