Search

[ ]of writing, it is unclear whether this will result in a permanent change in how blood sampling for clinical trials and routine healthcare are performed, although it seems unlikely that the progression of these sampling technologies will be slowed by the current situation Many of the early publications in this area had a primary focus on the development of blood sampling technologies, validation of bioanalytical methods and were limited to applications supporting nonclinical and clinical studies for pharmaceutical drug development Bioanalysis 7(16) (2015) https://www future-science com/toc/bio/7/16 Neil Spooner: Spooner Bioanalytical Solutions Ltd, Hertford, UK and School of Life and Medical Sciences, University of Hertfordshire, UK Melanie Anderson: Merck and Co , Inc , West Point, PA 19486, USA Enaksha R Wickremsinhe: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA

This is a guest editorial by Ramesh Durvasula, information officer for research at Lilly Research Laboratories. It is adapted from the article “Safety in Numbers: Connecting the Community to Improv...

Dr Bowsher is currently a senior research advisor at AIT Biosciences advising on technical, regulatory and business development matters related to bioanalysis of biotherapeutics, as well as maintaining his consultancy and laboratory businesses at B2S Consulting® (IN, USA), and B2S Labs (IN, USA), respectively. Formerly working at EMD Millipore’s BioPharma Services for 10 years and at Lilly Research Laboratories for 30 years, Dr Bowsher brings more than 40 years of experience in the pharmaceutical/biotech and CRO industries. He received a bachelor’s degree in chemistry from Indiana University (IN, USA), and holds a master’s degree and doctorate in biochemistry from the Indiana University School of Medicine. He is an adjunct assistant professor of biochemistry and molecular biology at the Indiana University School of Medicine. Since 1980, he has published more than 100 research papers and monographs, and 105 abstracts, as well as holding three patents. In 2001, Dr Bowsher founded and organized the Ligand Binding Assay Bioanalytical Focus Group (LBABFG) within the American Association of Pharmaceutical Scientists (AAPS) and in 2004 he was elected as an AAPS Fellow, as well as being awarded an AAPS Presidential Citation for his work in establishing an educational program, and has served as the co-organizer for the past 6 years of the highly successful AAPS Immunogenicity Training Course. In 2012, Dr Bowsher received the Distinguished Alumnus Award, School of Science, Indiana University-Purdue University (IN, USA). In March 2013, Dr Bowsher spoke to Alexandra Sklan at Bioanalysis regarding his bioanalytical career, involvement in the AAPS and the future outlook relating to macromolecule bioanalysis. His primary research interests are the development and validation of ligand binding assays for the bioanalysis of macromolecules, endogenous compounds and conventional xenobiotic drugs to support regulatory-compliant assessments of PK/TK, PD and safety, and the ADME of biotherapeutics.

Microsoft cofounder Paul G. Allen, who died from complications of non-Hodgkin’s lymphoma in October, is expanding his legacy in life sciences research with a $125 million donation to launch the Allen Institute for Immunology. The center, which will recruit about 70 scientists to study the human immune system, will join the Allen Institute for Brain Science and the Allen Institute for Cell Science in Seattle. Unlike the brain and cell institutes, which prioritize research like developing brain maps and cell atlases, the immunology institute will pair basic science with clinical research right off the bat. “You are hard pressed to study the human immune system and not get very close to disease in a hurry,” says Allan Jones, CEO of the Allen Institute. Jones recruited Thomas F. Bumol, a former executive at Lilly Research Laboratories, to lead the new institute, which will partner with five academic and medical centers in

This review will chronicle the genesis and the next fifty years or so of the Isotopic Chemistry effort at Eli Lilly and Company. It all began from a seed planted in Bob McMahon's mind while a post-doctoral fellow at MIT in 1949 and was later cultivated when he joined the Lilly Research Laboratories in 1954. From the humble beginnings of a few part-time radiochemists/part time metabolism scientists (Bob McMahon and Hugh Sullivan), the group has evolved to the eleven dedicated scientists that we have today. Copyright © 2007 John Wiley & Sons, Ltd.

PurposeThe purpose of this paper is to share the successful experience of Lilly Research Laboratories (LRL) in engaging senior leaders in developing the next generation of leaders.Design/methodology/approachThe paper describes the principles and approach used by LRL. It provides a straightforward description of the major leadership development programs with a more detailed description of a course on inspirational leadership. One of the co‐authors, a Vice President of Medical, describes his personal motivation for participating.FindingsThe commitment of a significant amount of time to their development by respected senior leaders is a powerful message and model to participants. The ability to interact in a deeply personal way with senior leaders is highly motivating to participants. The involvement of senior leaders in the design and development of programs gives them a strong interest in later participation. Being identified as an inspirational leader and having the opportunity to influence the next generation are personally rewarding to senior leaders.Originality/valueLRL is one of too few organizations that have succeeded in gaining a high level of commitment from senior leaders to developing future leaders; their methodology may be valuable to other large and medium‐sized organizations.

This review highlights the discovery and development of chemotherapy at Eli Lilly & Company over the past 30 years from the Vinca alkaloids-vincristine, vinblastine, and vindesine-to targeted therapy. During the late 1970s, Lilly began an exploration of new synthetic compounds based on solid tumor screening models. Several novel antimetabolites with the potential to treat solid tumors were identified. Two such agents, gemcitabine and pemetrexed, underwent clinical development and are now among Lilly's portfolio of approved anticancer drugs. Gemcitabine, a pyrimidine nucleoside that has a profound effect on DNA synthesis, has been approved for the treatment of pancreatic, non-small cell lung, bladder, and most recently, breast, and ovarian cancer. Pemetrexed, a novel antifolate with potent cytotoxic effects, is distinguished from other antifolates by virtue of its ability to inhibit multiple folate-dependent enzymes. Pemetrexed, given in combination with cisplatin, has been recently approved for the treatment of malignant pleural mesothelioma and as second-line treatment for non-small cell lung cancer. Spurred by advances in the understanding of cancer as a disease process, Lilly's anticancer drug program began to transition to a more "targeted" approach during the 1990s. These efforts have recently culminated in the identification and development of enzastaurin, a PKCbeta inhibitor with potent anti-angiogenic properties. Enzastaurin has shown promising single-agent activity in patients with relapsed diffuse large B-cell lymphoma and recurrent glioblastoma multiforme, and is an excellent candidate for combination with cytotoxic agents.

Behiye Ozcan, Sebastian J C M M Neggers, Anne Reifel Miller, Hsiu-Chiung Yang, Virginia Lucaites, Thierry Abribat, Soraya Allas, Martin Huisman, Jenny A Visser, Axel P N Themmen, Eric J G Sijbrands, Patric J D Delhanty and Aart Jan van der Lely Department of Medicine, Erasmus University MC, 3000 CA, Rotterdam, The Netherlands, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA and Alize Pharma, 69 130 Ecully, France

Eli Lilly & Co. cut the ribbon last week on immuno-oncology labs for 40 researchers at the Alexandria Center for Life Science, a two-tower life sciences research facility on the East River in Manhattan. Lilly, the anchor tenant at the Alexandria Center, arrived in 2010 and added a second bank of labs in 2015 focused on immune-system oncology. Jan M. Lundberg, president of Lilly Research Laboratories, said the newest labs are intended to make the company’s research more “efficient and competitive” and to locate it “in an environment in which, just outside our center, are tremendous opportunities to collaborate with leading clinical centers.” The center’s neighbors include Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine.

Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA Departments of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, MO 63110, USA Scios, Inc., Sunnyvale, CA 94086, USA

For the past 25 years, I have devoted most of my research efforts to the application of molecular genetics to yield improvement and production of novel secondary metabolites in actinomycetes. My group at Lilly Research Laboratories worked with a variety of Streptomyces species and with strains of Amycolatopsis and Saccharopolyspora. We developed molecular genetic tools to manipulate actinomycete genes, and applied them to important secondary metabolites, including tylosin, daptomycin, vancomycin, chloroeremomycin, and spinosyns. In the early years, I helped establish recombinant DNA technology to manufacture mammalian proteins, and more recently, helped implement microbial genomics as a research tool for antibiotic discovery. In this paper, I review some highlights, primarily from the actinomycete work. Journal of Industrial Microbiology & Biotechnology (2000) 24, 79–88.

ADepartment of Energy report released in 1987 stated in a visionary prediction that “Knowledge of the human genome is as necessary to the continuing progress of medicine and other health sciences as knowledge of human anatomy has been for the present state of medicine” (Barnhart 1989). The pursuit of this knowledge has marked an era of rapid genomics-based discovery that continues to yield unique insights into connections between disease and molecular factors. One key method for transforming these initial insights into direct evidence of disease pathogenesis is molecular imaging. Imaging techniques that have been customized for laboratory animals provide scientists with the unprecedented ability to link detailed molecular understanding with the complexity of whole organism physiological responses and anatomical detail. The advancement of knowledge derived from the mammalian genome is likely to depend on the context provided by the unique blending of our knowledge of anatomy with the translational application of imaging technology. The primary objective of this ILAR Journal issue focused on laboratory animal imaging is to provide readers with a compendium of reviews that describe the methods, the limitations, and a few examples of the most common applications of small animal imaging to human disease. Because most disease processes are dynamic, there are inherent limitations to using static tissue-based techniques to study dynamic processes. Among these is that a large number of animals is needed for every experiment to enable the processing of tissue at given time points of interest, and histopathological examination of these tissues using standard microscopy is a daunting task. In addition, there is a degree of variability introduced when the control level of a factor is determined by comparing different animals instead of using each animal as its own control. Experimental designs of longitudinal studies pose particular limitations because a certain degree of understanding about the kinetics of a disease process is critical to the appropriate timing of tissue collections. The imaging modalities available for use with laboratory animals provide a means to explore the molecular mechanism of several diseases, minimize many of the limitations of static tissue-based techniques, and, most importantly, decrease the numbers of animals required. In fact, depending on the application, it is possible to reduce the number of animals required per study by as much as 80% to 90%. This feature is noteworthy because, perhaps unique to the ILAR Journal, there is an intentional effort to publish reviews that include considerations specifically relevant to animal care and use. The first article, by Brenda Klaunberg and Judith Davis, presents an overview of key considerations for laboratory animal imaging center design. This review not only is relevant to readers considering new facility design but also can provide a series of quick checks for existing centers as well as strategies for improvement. Contributing authors Isabel Hildebrandt, Helen Su, and Wolfgang Weber then discuss anesthesia for in vivo imaging of small animals in the context of how animal preparation differs among imaging modalities, and how the imaging procedures themselves can affect animal physiology. A general overview of practical considerations in rodent cardiac imaging is provided by Kennita Johnson as a segue to detailed reviews of specific imaging techniques. This article is a good source of baseline information about the particular challenges of cardiac imaging. The contributions of imaging technology to the biomedical sciences are incontrovertible. In fact, one has only to list the number of Nobel prizes awarded to scientists in nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) to appreciate the importance and recognition this field has received. These include the 2003 Nobel Prize for Physiology and Medicine awarded to Paul Lauterbur and Peter Mansfield for the development of MRI. Earlier NMRrelated Nobel Prizes were awarded for Chemistry (Kurt Wuthrich in 2002, Richard R. Ernst in 1991) and Physics (Felix Bloch and Edward M. Purcell in 1952 and Isidor I. Rabi in 1944; http://nobelprize.org). The first manuscript describing the MRI of a rat was published almost 25 years ago, and the technique continues to evolve and expand the scientific advances made possible Myrtle A. Davis, DVM, PhD, is a Research Advisor in Toxicology, Drug Disposition, and Pharmacokinetics at Lilly Research Laboratories in Greenfield, Indiana. Address correspondence and reprint requests to Dr. Myrtle Davis, Toxicology, Drug Disposition, and Pharmacokinetics, Lilly Research Laboratories, 2001 W. Main Street, Greenfield, IN 46140 or email davisma@lilly.com.

a Uni6ersity of California, San Diego, La Jolla, CA, USA b Emory Uni6ersity School of Medicine, 69 Butler Street, S.E., Atlanta, GA 30303, USA c Uni6ersity of California, San Francisco, San Francisco, CA, USA d Uni6ersity of Michigan, Ann Arbor, MI, USA e Royal Brompton Hospital and Imperial College, School of Medicine, London, UK f Uni6ersite Libre de Bruxelles, Brussels, Belgium g Lilly Research Laboratories, Indianapolis, IN, USA

Summary Background The discovery and clinical development of new drugs to treat cancer at Lilly Research Laboratories has undergone significant change during the past 15 years. During the early 1980s drug discovery relied heavily on a panel of syngeneic murine solid tumour models to identify new agents for clinical trial. New classes of oncolytic agents identified by this methodology include the difluoronucleoside antimetabolites, diarylsulfonylureas, and a series of folate-based enzyme inhibitors. Within the folate-based discovery programme at Lilly, a broad understanding of the structure activity relationships of folate antimetabolites and the biochemical basis of folate transport, processing, and enzyme inhibition has enabled a more rational approach for drug discovery. Current studies Folate receptor binding properties are being studied to predict tumour sensitivities and tissue toxicities. This information, together with knowledge of a compound's ability to undergo polyglutamation via the enzyme folylpolyglutamate syn-thase, assist in the more rational selection of agents with designed cellular selectivities. Ultimately, the complex metabolic pathways involving folate metabolism provide numerous targets for enzyme inhibition. Inhibitors of purine biosynthesis and thymidylate synthesis have demonstrated broad activity in preclinical models of disease including several human tumour xenografts, and are undergoing clinical testing. The folate-based drug discovery programme serves as a model for other biochemically based drug discovery programs including those based in drug resistance, signal transduction and cell cycle control.

Cellular in vitro assays have been both developed and employed by us to search for new, solid tumor specific anticancer agents. Parallel in vivo models are then used to assess the therapeutic efficacy of candidates selected by the in vitro assays. During the past 4 years, extracts as well as pure compounds from natural products have been obtained from collaborators at the University of Hawaii and Lilly Research Laboratories. The samples have been analyzed, the structures identified and a number of lead compounds proposed

Synchrotron X-ray sources provide the highest quality crystallographic data for structure-guided drug design. In general, industrial utilization of such sources has been intermittent and occasionally limited. The Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline provides a unique alternative to traditional synchrotron use by pharmaceutical and biotechnology companies. Crystallographic experiments at LRL-CAT and the results therefrom are integrated directly into the drug discovery process, permitting structural data, including screening of fragment libraries, to be routinely and rapidly used on a daily basis as part of pharmaceutical lead discovery and optimization. Here we describe how LRL-CAT acquires and disseminates the results from protein crystallography to maximize their impact on the development of new potential medicines.

Barbara E. Laughon, H. S. Allaudeen,* Jeffrey M. Becker, William L. Current, Judith Feinberg,* Jacob K. Frenkel, Richard Hafner, Walter T. Hughes, Catherine A. Laughlin, Joel D. Meyers, Lewis K. Schrager, and Lowell S. Young Developmental Therapeutics Branch of the Basic Research and Development Program, Medical Branch of the Treatment Research Program, Epidemiology Branch of the Division of AIDS, and Antiviral Research Branch of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland; Department of Microbiology, University of Tennessee, Knoxville, and Department of Infectious Diseases, St. Jude Children s Research Hospital, Memphis, Tennessee; Lilly Research Laboratories, Indianapolis, Indiana; Department of Pathology, University of Kansas Medical Center, Kansas City; Department of Infectious Diseases, Fred Hutchinson Cancer Research Center, Seattle, Washington; Kuzell Institute for Arthritis and Infectious Diseases, San Francisco, California

Background: Between 54%-85% of pediatric patients (pts) with ALL can be cured by definitive chemotherapy protocols. HSCT may be considered for high-risk pts after induction therapy or for refractory/relapsed pts. However, HSCT is recognized as a highly specialized, costly and resource intensive procedure requiring ongoing care over months to years. HSCT is associated with significant life-threatening complications with transplant related mortality of 20-30% and acute/chronic graft vs. host disease and infections. The objective of this study was to assess the economic burden up to 5 years of pediatric pts with ALL who received HSCT from the US commercial payers' perspective. Method: Pediatric pts ( Results: A total of 209 pediatric ALL pts were identified. Mean age was 10 years and 43.1% of pts were female. The median follow-up period after the index date was 1.3 years. During the 6 months prior to the index date, pts incurred average total healthcare costs of $287,001. The median duration of the initial hospitalization for the HSCT was 41 days (interquartile range 32-55). Over the five years following the index date, results showed substantial HRU and costs associated with the HSCT. The most intensive HRU and highest healthcare costs were observed within the first year following the index date; pts had an average of 49 days with outpatient (OP) visits, 29 days with OP laboratory services, and 68 inpatient (IP) days corresponding to 3.10 IP admissions (including the hospitalization for the first HSCT) and incurred mean total healthcare costs of $683,099 (median of $511,021) (Figure 1 and 2). Costs associated with the first HSCT hospitalization represented 62.4% of the total costs incurred during the first year. Although a decreasing trend was observed over time, HRU and costs remained high; 28.8% of pts had at least one IP admission at year 2, 19.6% at year 3, 20.0% at year 4, and 6.7% at year 5 (Figure 1). The number of days with OP visits and the number of days with laboratory services also remained high over time (Figure 1). The average total healthcare cost was $104,584 (median of $21,877) at year 2, $79,092 (median of $11,000) at year 3, $106,334 (median of $10,426) at year 4 and, and $38,291 (median of $10,082) at year 5 (Figure 2). Our results also showed high variation in healthcare costs across pediatric pts following the index date; 29.4% of the total costs (over the entire sample) in year 1 were incurred by the 10% pts with the highest costs. Starting from the second year, the 10% of pts with the highest costs accounted for 61.3 to 76.6% of the total costs for each year, suggesting that a small proportion of pts still incur very high costs several years after HSCT. Conclusions: Healthcare resource utilization and direct costs associated with allogeneic HSCT are substantial with the first year direct cost alone of $683,099 with substantial costs over the following years. Further studies are needed to understand the humanistic and financial burden of HSCT for pediatric pts and their caregivers. Figure 1. HRU after Index Date Figure 1. HRU after Index Date Figure 2. Total Healthcare Costs after Index Date Figure 2. Total Healthcare Costs after Index Date Disclosures Maziarz: Athersys: Consultancy, Patents & Royalties, Research Funding; Novartis: Consultancy. Guerin:GlaxoSmithKline, Janssen Scientific Affairs, Janssen-Ortho, Inc., Merck & Co., Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ogilvy Renault, Ortho-Clinical Diagnostics, Inc., Otsuka America Pharmaceutical, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Pfizer Canada, Inc., RX&D, Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratories, Bayer Healthcare Pharmaceuticals, LLC, Celgene Corporation, Cempra Inc., Centocor Ortho Biotech, Cooley LLP, Cyberonics, Inc., DLA Piper, Eli Lilly & Company,Forest Laboratories, Inc., Genentech, Inc.,: Consultancy, Other: Annie Guerin is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Gauthier:AbbVie Inc., Celgene Corporation, Eli Lilly & Company, Genentech, Inc. ,GlaxoSmithKline, Janssen Scientific Affairs, LLC, Novartis Pharmaceuticals Corporation, Pfizer Canada, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Sunovion Pharmaceuticals Inc.,Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Genevieve Gauthier is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Heroux:AbbVie Inc., Alcon Laboratories, Celgene Corporation, Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation, Shire Pharmaceuticals Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Julie Heroux is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Zhdanava:AbbVie Inc., Genentech, Inc., Merck Frosst Canada, Novartis Pharmaceuticals Corporation,Shire Pharmaceuticals Inc., Takeda Pharmaceuticals U.S.A., Inc.: Consultancy, Other: Maryia Zhdanava is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Wu:Molecular Insight Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Ortho McNeil Pharmaceuticals, Inc., Sanofi, Savient Pharmaceuticals, Inc., Shire Pharmaceuticals Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Takeda Global Research & Development Center, Inc., Takeda Pharmaceuticals U.S.A., Inc., TAP Pharmaceutical Products, Inc., Vertex Pharmaceuticals Incorporated: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Janssen Pharmaceutica, Inc., Janssen Scientific Affairs, LLC, Lilly Research Laboratories, McNeil Consumer & Specialty Pharmaceuticals, MedImmune, LLC, Melinta Therapeutics, Inc., Millennium Pharmaceuticals, Inc.,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; Celgene Corporation, Centocor Ortho Biotech, Cephalon, Inc., ConvaTec Inc., Corus Pharma, Inc., Eli Lilly & Company, Eli Lilly & Company, Ethicon, Inc., Forest Laboratories, Inc., Genentech, Inc., GlaxoSmithKline, Janssen Global Services, LLC,: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations; AbbVie Inc., Alcon Laboratory, Astellas Pharma Inc., Astellas Pharma US, Inc., AstraZeneca, Barger & Wolen LLP, Bayer Healthcare Pharmaceuticals, LLC, Biosense Webster, Inc., Blue Cross Blue Shield Association, Boehringer Ingelheim, Bristol-Myers Squibb C: Consultancy, Other: Eric Q Wu is an employee of Analysis Group Inc, which has received consultancy fees from the listed organizations. Thomas:Novartis: Employment. Chen:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership, Other: Lei Chen is an employee of and owns stocks/options of Novartis Pharmaceuticals Corporation, the sponsor of this study.

LY333328 is a novel glycopeptide from Lilly Research Laboratories which is claimed to have activity both in vitro and in vivo against vancomycin-resistant enterococci. Information on this compound has been published at three recent meetings, the 7th European Congress of Clinical Microbiology and Infectious Diseases (March 26 - 30, Vienna, Austria); On the Frontier of Antibacterial Drug Discovery (April 27 - 28, Princeton, USA); and the 19th International Chemotherapy Congress (July 16 - 21, Montreal, Canada). This update draws together the published data and attempts to assess the potential therapeutic use of this interesting new compound.

With the intention of bringing together leading academic researchers, industry scientists, business development experts and scientific policy makers, the Society for Medicines Research (SMR) hosted a highly engaging and thought-provoking meeting entitled "Partnerships: Future Models for Drug Discovery" at the Lilly Research Centre in Windlesham, Surrey. With the challenges to discover and develop innovative and differentiated new medicines having never been greater and with many questions arising around the viability of current pharmaceutical business models, this meeting offered the opportunity to explore potential new ways to bring innovation and productivity to the drug discovery sector. Through a series of presentations from leading figures from across the public and private sector, the conference aimed to explore novel business models for research and development and to discuss on the changing dynamics around the interactions between traditional models for academia, industry and funders. Copyright © 2013 Prous Science, S.A.U. or its licensors. All rights reserved.

Jean Ferrieres [Orateur] (1), Guy Berkenboom (2), Zdenek Coufal (3), Stefan James (4), Attila MohaCsi (5), Gregory Pavlides (6), Kirsi Norrbacka (7), Magali Sartral (8), Marie-Ange Paget (8), Molly Tomlin (9), Uwe Zeymer (10) (1) CHU Rangueil, Cardiologie B, Toulouse, France – (2) ULB Erasme University Hospital, Department of Cardiology, Brussels, Belgium – (3) Batova Krajska Nemocnice Zlin, Department of Cardiology, Zlin, Republique Tcheque – (4) Uppsala University Hospital, Dept. of Cardiology and Uppsala Clinical Research Center, Uppsala, Suede – (5) Gottsegen Institute of Hungarian Cardiology, Budapest, Hungaria – (6) Onassis Cardiac Surgery Center, Kallithea, Grece – (7) Lilly Research Laboratories, Eli Lilly and Company, Vantaa, Finlande – (8) Lilly Research Laboratories, Eli Lilly and Company, Paris, France – (9) Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, United-States – (10) Klinikum Ludwigshafen, Ludwigshafen, Allemagne

G. Umpierrez, T. Blevins, J. Rosenstock, C. Cheng, E. Bastyr, J. Anderson 1 Emory University School of Medicine, Division of Endocrinology, Atlanta, USA 2 Texas Diabetes and Endocrinology, , Austin, USA 3 Dallas Diabetes and Endocrinology Center, , Dallas, USA 4 Eli Lilly and Company, Lilly Research Laboratories, Indianapolis, USA 5 Eli lilly and Company, Lilly Research Laboratories, Indianapolis, USA

Hyung Ki Choi, Je Jong Kim, Sae-Chul Kim, JunKyu Suh, Yoon Kyu Park, Seong Choi, Woong Hee Lee, Ki Hak Moon, Hae Young Park, Jong Kwan Park, Wei Christine Wang, Vladimir Kopernicky From the Department of Urology, Yongdong Severance Hospital, Seoul, Korea University Ansan Hospital, Ansan, Chungang University Hospital, Seoul, Inha University Hospital, Incheon, Kyungpook University Hospital, Daegu, Kosin University Hospital, Busan, Dong Seoul Hospital, Seoul, Yeungnam University Hospital, Daegu, Hanyang University Hospital, Seoul, Chonbuk National University Hospital, Jeonju, Korea, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA, Lilly Area Medical Center, Vienna, Austria

This is the first special topic volume, collected from articles within Progress and Drug Research dealing with new antiviral agents. The editors have chosen an important range of topics – concentrating on only one aspect of HIV (a good idea given the breadth of antivirals for HIV), and agents for influenza, hepatitis C, hepatitis B, herpesviruses and picornaviruses. Although the range of topics is broad, most of the authors come from pharmaceutical companies, particularly the Lilly Research Laboratories at Eli-Lilly in Indianapolis. In fact, authors of four of the six chapters are members of the Eli-Lilly Research Laboratories, one is from the Roche Research Laboratories in Hertfordshire, and one from the University of Southern California. The reviews all tend towards academic discussion of the pharmacologic uses of drugs. Further, all the authors approach the subject from the point of view of drug design and use, rather than from a clinical standpoint with drug design based upon response to clinical needs. This is not a criticism of the authors' approach, but readers need to be aware that emphasis is more on biochemical rather than clinical drug design. In general, the chapters deal with important issues, and have brief summaries of the virology at the start, followed by more detailed discussion of different types of drug classes, and individual representatives of these classes. Who would find this book useful? The book is very much aimed at a specialist reader with knowledge of pharmacology, rather than a clinical audience. The discussion of HIV protease inhibitors is good, although the rapid change in HIV therapy means any book chapter will be rapidly out-of-date. The chapter on influenza drugs was excellent, although more discussion of the use of these agents in pandemic situations (such as arose with H5 influenza in Hong Kong during 1997) would be of interest. The discussion of hepatitis C was useful, although the evolution of treatment of hepatitis C means multi drug therapy is now standard, and it would be useful to have further discussion of what may be next. Furthermore, recent developments in the treatment of acute HCV infection, and new indicators of response to treatment, mean this chapter lacked discussion of some evolving and important areas. The chapter on herpesviruses dealt with the basic issues well, although several areas of treatment such as the use of valganciclovir, intravitreal ganciclovir, and animal models for testing of herpesviruses were deficient. It was disappointing not to see some discussion of vaccines as there has been considerable literature regarding vaccination, particularly for HSV infection, particularly in the last three years. The picornavirus chapter was adequate, although there was less discussion of drugs such as pleconaril (which is now in limited clinical use) than would be useful to the general reader. Overall, the specialist pharmacologist, or a clinician interested in a particular area of antiviral research, would do well to start with one of these chapters relating to their area of interest. The major weakness of the book is the rapid rate of advance in antiviral therapy – particularly for HIV, hepatitis C and the herpesviruses. This will be a weakness of any book, although the provision of addenda immediately prior to publication can be of use in reducing this problem. What I liked about this book was the excellent overall structure, dealing with the most important antivirals available in 2001. Selection of one area of HIV therapy for more detailed discussion was a wise choice, and utilization of review style articles to make up the book, made for in-depth reading. The problems with this book were that in many areas it was incomplete (such as for anti viral agents for herpesviruses), the lack of any significant reference to vaccination, and the dense nature of the material. The book would benefit from more summary tables for occasional readers. It was striking that new vaccines for influenza (adjuvanted, intranasal, and others), HSV, and HIV were not mentioned. The referencing style, where article titles were not given was also annoying, given that a target audience for this book may well look to the references for further information about particular areas that they find of interest within each chapter. Overall, Antiviral Agents: Advances and Problems is a reasonable book in a difficult field. The information is readable, the authors provide significant detail in the areas they cover, and the references are in general inclusive. It would be a useful book for the reader looking for a succinct introduction to one of the six major areas covered in the chapters, or looking for further information about the pharmacology of these antiviral agents.

A list is presented of cultures of algae available for purposes of research and teaching. The list includes 753 Chlorophyta; 94 Chrysophyta; 56 Cyanophyta; 55 Euglenophyta; 7 Pyrrophyta; 6 Rhodophyta; 1 species of Phaeophyta; and 5 residual flagellates. Formulae of culture media and directions for maintaining the cultures are included, as are instructions for evoking the sexual process in species of Chlamydomonas, Astrephomene, Pandorina, Eudorina, Cosniarium, Closterium, 0edogonium, Bulbochaete, and Vaucheria. THE CULTIVATION of algae has shown rapid progress in the last two decades due to the increasing awareness of their usefulness as materials in physiological and genetic research, as well as in basic studies in morphology, taxonomy, cytology, and ecology, where the availability of large clonal populations is often of prime importance. The desirability of preserving algal strains which have been used in investigations and the need by investigators for a source of algal strains for research prompted the establishment of a culture collection of algae at Prague, and later at Cambridge University, by Dr. E. G. Pringsheim. Smaller collections in Paris, Basel, and other laboratories both in Europe and the United States included some algal cultures, but onily in the Cambridge Collection was there a variety of cultures which, upon payment of a small fee, were readily available to any worker. It was felt that for safety and convenience, especially on the part of the investigators in the United States, a collection similar to that at Cambridge should be established in the United States. Accordingly, the Culture Collection of Algae at Indiana University was established in the Department of Botany in 1953, using a nucleus of cultures obtained from the Culture Collection of Algae and Protozoa at Cambridge University. The Research and Equipment Committees of Indiana University provided funds for the installation of physical facilities for the cultivation of algae. Funds for materials and technical assistance were given by the Lilly Research Laboratories of Indianapolis during 1953-1955 and by the Charles F. Kettering Foundation of Yellow Springs, Ohio, during 1955-1959. The National Science Foundation, through Grant NSF G11027, has provided funds for a full-time curator since February 1, 1960, and through Grant NSF GB-1689 has permitted the purchase and installation of laboratory furniture for expanded laboratory facilities for the Collection in 1963-1964. The National Institutes of Health activated on February 1, 1965, Grant PHS FR 00141 01 to provide for a study of longterm preservation of algal stocks and for the 1 Received for publication MWarch 30, 1964. The costs for excess pagination are being defrayed by the Culture Collection of Algae at Indiana University. isolation and characterization of new genetic stocks. Indiana University acknowledges with appreciation the support given by these organizations. Funds received from the sale of cultures cover the expenses of other employees, supplies, postage, and secretarial assistance. No charges are made by Indiana University for the use and maintenance of physical facilities. CULTURES FOR RESEAR CH-All cultures in the Collection are available to all interested individuals and organizations, both academic and commercial. To acadenmic institutions and nonprofit organizations the cost per culture is $2.002 postpaid; commercial organizations are charged $10.00 per culture postpaid. Cultures for research can usually be sent within 10 days after the receipt of the order. Investigators who use cultures from the Collection are requested to indicate the IU Collection numbers in their publications in order to identify their strains more exactly. Reprints of such publications will be appreciated. Investigators using newly isolated algal strains in their researches are invited to send their strains to the Collection at any time they may have no objection to unrestricted distribution to other workers. Mutant strains will be added to the Collection only if they have been characterized. The final decision on the addition of any strain to the Collection must be reserved for the Director. CULTURES FOR TEACHING-Although the Collection was established primarily to serve as a source of cultures for research, the urgent need for cultures of living algae in teaching is recognized. Please see the section at the end of the culture list for details of the reduced rates for certain cultures selected for use in the classroom. ORDERS-Orders for cultures for research and for teaching should be addressed to the Culture Collection of Algae, Department of Botany, Indiana University, Bloomington, Indiana. Requests by personal letters or by telephone (Area Code 812; 337-5353) will be filled with invoicing delayed, if desired, until after receipt of official confirming purchase orders. Payment should be made to Indiana University only after the receipt of invoice forms issued-by the Culture Collection. 2 Prices in effect beginning January 1, 1965; until that time, $1.00.

In June of 1962, it was my pleasure to present at the Third Annual Meeting of The Society for Economic Botany a plan for an unusual approach to the search for useful plants (1). It consisted of making greater use of major herbaria by extracting from them all unpublished label data which might be potentially valuable to man from the standpoint of health and medicine. I would like to report today on the realization of this plan at one major institution and on what appears to be a large windfall of possible food plants among our findings. The search to which I refer was carried out through the sponsorship of the Botanical Museum of Harvard University and consisted of a sheet by sheet examination of the estimated 2,500,000 specimens of flowering plants in the combined collections of the Arnold Arboretum and Gray Herbarium of that University.3 Two persons trained in herbarium techniques and working less than full time were able to complete the search in five years. The work was supported in turn by Smith, Kline & French Laboratories; the National Institute of Mental Health; and the Eli Lilly Research Laboratories. The information sought and recorded covered a broad range of data, including not only specific folk or native remedies but any notes allowing possible physiological activity. The search was undertaken in the belief that herbaria represent rich and untapped reservoirs of such information, which, in some instances, might provide the only remaining clews to medical materials of peoples the cultures of which already have been absorbed by civilization. We were eager also to recognize species which may not have been used by

The vinca alkaloids were discovered independently in two separate laboratories by a combinat ion of serendipity and what we have called rational broad spectrum tumor screening. In the first case, R. L. Noble and his colleagues in the Collip Labora tory at the University of Western Ontar io were examining extracts ofCatharanthus roseus G. Don ( Vinca rosea Linn.) for their effects on blood glucose because of unconfirmed reports in various parts of the world that the plant was being used for the treatment of diabetes. These investigators (4) found by chance observation that the extracts produced profound leukopenia in the rat, and they isolated an alkaloid which demonstrated such activity as a crystalline sulfate, which they named vincaleukoblastine (VLB). They speculated that it might have potential chemotherapeutic properties. This is the drug which is currently marketed as Velban ~'~ (vinblastine sulfate, Lilly). Unknown to the Canadian group, a group of investigators in the Lilly Research Laboratories had observed profound activity in extracts from the same plant against the P-1534 lymphocytic leukemia in DBA/2 mice and had isolated a second alkaloid with antileukemic activity which they named leurosine (3). We were also able to show that after VLB and leurosine were removed from the extracts that there were components remaining with profound ant i tumor activity. These were eventually identified as leurocristine (Oncovin, vincristine sulphate, Lilly) and leurosidine (12). The discovery in the Lilly Research Laboratories resulted from a privately funded ant i tumor screening program mounted in response to a national effort to increase the detection and development of new anticancer drugs through what was then the Cancer Chemotherapy National Service Center (CCNSC). We had long felt that harnessing the major pharmaceutical laboratories to a single set of tests or test systems would have been an error. It had been the experience of most such laboratories that, as new systems, tests, techniques, etc., are devised, a new class of agent was frequently found. The more varied the system in use, the greater the probability of different kinds of materials being detected. In the nationally organized program, the screening philosophy appeared to be based upon the concept of using as few detection systems as possible that would detect the largest number of drugs currently considered as having clinical activity. This was clearly an at tempt at a cost-effective approach. Our concern was that cancer was a heterogenous family of proliferative diseases, and that just as cancer drugs had tumor spectra, experimental neoplasms also had drug spectra. I f this were true, continuous use of a few or even single murine neoplasms for cancer screening might not be expected to detect new or novel drugs, much less predict for activity against a broad spectrum of neoplasms and histological types. While performing well in terms of detecting novel structures, our system did not predict

In the early autumn of 1924 we were invited by Professor A. A. Noyes, director of the Gates Chemical Laboratory of the California Institute of Technology, Pasadena, California, to investigate the chemical and other properties of insulin in his laboratory under a grant from the Carnegie Foundation. Commercial insulin as prepared by the Lilly Research Laboratories of Eli Lilly and Company, Indianapolis, Indiana, has served as the material for our investigation. Two forms of commercial insulin have been used by us; one a dry powder evaluated at approximately 8 rabbit units per milligram; the second a highly concentrated aqueous solution (2.44 per cent. solids) containing approximately 300 rabbit units per cubic centimeter, and with 120 milligrams of hydrochloric acid per 100 cubic centimeters.

SINCE PHENYLKETONURIA, a metabolic anomaly associated with mental retardation, can now often be beneficially treated with a phenylalanine-free diet, it has become desirable to detect its presence as early as possible, since the diet loses its efficacy as the child grows older. At the suggestion of one of us (J.W.) both the Lilly Research Laboratories of Indianapolis, Ind., and later the Ames Company, Inc., of Elkhart, Ind., developed test papers for the detection of phenylketonuria. These small strips of prepared paper may be used by immersion in a fresh urine specimen or by simple pressure against a wet diaper. The Lilly test paper* was released as RT 974 for clinical trial purposes only. The Ames reagent strips are being marketed under the name of Phenistix. The work reported in this paper was done with the Lilly material, but the Phenistix are almost identical in application. With the Lilly test paper the presence of phenylpyruvic acid in the urine produces a color change from the original yellowish white to a blue of varying density, depending on the amount of phenylpyruvic acid present. Amounts as small as 15-20 mg per 100 cc of urine are detectable by this method. The test is not, however, specific for phenylketone; the following substances may also induce color changes as follows: phenol, blue; pyruvic acid