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 Concise BioPharmaceutical Glossary & Taxonomy
Evolving Terminology for Emerging Technologies
Comments? Questions? Revisions? Mary Chitty mchitty@healthtech.com
Last revised March 28, 2008

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About this glossary   Basic genetics & genomics: What's the difference? 

adverse drug reaction ADR:  ADRs may include drug interactions as one of many causes but the reverse is not true. The reader is cautioned regarding usage of drug reaction terms as multiple nearly- similar terms of varying granularity abound. .. "An adverse reaction to a drug has been defined as any noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment(2). However, WHO's original definition of ADR excluded therapeutic failures, intentional and accidental poisoning and drug abuse, as well as adverse events due to medication errors such as drug administration or non- compliance(1) ... Due to non- uniform usage of these terms, it is sometimes difficult to compare various studies and derive incidence rates, etc. for ADRs, and Drug Interactions. Saeed A Khan, "Drug Interaction or Adverse Drug Reaction? Confusing Terms", British Medical Journal 10 July, 1998 http://bmj.com/cgi/eletters/316/7149/1930

Alternatively: ADE Adverse Drug Event

adaptive clinical trials: A process for improving the efficiency of clinical trials based on interim analyses of clinical data, potentially leading to reductions in overall sample size, shorter project duration, improved quality of results, and reduced costs. Tufts Center for the Study of Drug Development, Glossary of terms, 2006 http://csdd.tufts.edu/InfoServices/Glossary.asp

Tools such as toxicogenomic assays can provide important information about a drug's effectiveness and safety. An adaptive trial would generate and incorporate such information to help guide the more effective use of medicines. In an adaptive trial, for example, patient outcomes could be used as they became available to adjust the allocation of future patients or some other aspect of the study design. Adaptive Clinical Trials are a stepping stone toward Personalized Medicine,  PharmaWeek, July 10, 2006 http://www.healthtech.com/news/strategic_briefings/2007/When%20Smaller%20is%20Better.asphttp://www.pharmaweek.com/Regulatory_And_Legal/Adaptive%20Clinical.asp 

Within the past few years many new approaches have been developed to address this goal, e.g., adaptive trial design, Bayesian analysis, and the use of biomarkers. Adaptive Clinical Trial Designs, Oct. 2007, Toronto 

ADMET Administration, Dosage, Metabolism, Elimination, Toxicology:  We know a lot about A and M, not so much about D and E.

Alternatively ADME/Tox.  Related terms: bioequivalence, drug disposition, pharmacodynamics, pharmacokinetics

alternative splicing:   The production of two or more distinct mRNAs from RNA transcripts having the same sequence via differences in splicing (by the choice of different exons). Mouse Genome Informatics http://www.informatics.jax.org/javawi2/servlet/WIFetch?page=glossaryIndex&print=no 

analyte specific reagents: A new class of regulated product: analyte specific reagents. These products are usually a singular reagent, such as an antibody, which can be used toward developing a test by third parties, such as another company or a hospital. The manufacturer of this product is not planning to sell it as part of a kit, but only as an independent reagent. Therefore, it is of low risk to the user, it can be exempt from 501(k) [device] requirements, and by definition must be used "for identification and quantification of an individual chemical substance or ligand in biological substances." Joseph Hackett, FDA  in CHI Summit Pharmacogenomics Report

antisense (molecule): An oligonucleotide or analog thereof that is complementary to a segment of RNA or DNA and that binds to it and inhibits its normal function. IUPAC Medicinal Chemistry

Molecular biologists describing DNA sequences or referring to one of the two strands of double- stranded DNA frequently use complementary pairs of terms, such as coding/ non- coding, sense/ nonsense or transcribing/ non- transcribing. Unfortunately none of these pairs is defined in a universally accepted way…Of the three pairs of terms mentioned, NC- IUB and JCBN believe coding/ non- coding to be preferable. Moreover, as the word 'coding' refers to the relationship between nucleic acids and proteins, rather than the mere transcription of DNA into RNA, it is logical to call the strand with the mRNA sequence the coding strand, as in the first example. When DNA sequences are described by giving the sequence of only one strand, this is usually the strand with the same sequence as the RNA (messenger, ribosomal, transfer, etc.) and should therefore be called the coding strand. [JCBN/ NC- IUB Newsletter, Joint Commission on Biological Nomenclature and Nomenclature Commission of IUB, 1989]  http://www.chem.qmw.ac.uk/iubmb/newsletter/misc/DNA.html  

Narrower terms: antisense DNA, antisense oligonucleotides, antisense RNA.  Related terms: RNAi; missense mutation, nonsense mutation; ribozymes

antisense DNA: DNA that is complementary to the sense strand. (The sense strand has the same sequence as the mRNA transcript. The antisense strand is the template for mRNA synthesis.) Synthetic antisense DNAs are used to hybridize to complementary sequences in target RNAs or DNAs to effect the functioning of specific genes for investigative or therapeutic purposes. MeSH, 1991  

antisense oligonucleotides: Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize. MeSH, 1991

An oligonucleotide that has a complementary sequence to a portion of, or to all of, an mRNA. Being complementary to a particular target mRNA, antisense oligonucleotides bind specifically to that mRNA; the proprietary chemical modifications made to the antisense molecules facilitate tight binding. When binding occurs, the ability of the mRNA to be read by the cell’s translational machinery is inhibited, and synthesis of the protein that it encodes is blocked. Unlike a gene knockout, this inhibition requires the continuous presence of the antisense molecule; thus, it is reversible. A great advantage of antisense technology is that researchers can design specific inhibitors of a gene of interest based only on knowledge of the gene sequence.

apoptosis: One of the two mechanisms by which CELL DEATH occurs (the other being the pathological process of NECROSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and  appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA FRAGMENTATION) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. MeSH, 1993

If someone could figure out how to make fat cells undergo apoptosis (without harmful side effects) they could make a bundle. 

Related terms: programmed cell death

attrition  Early attrition of poor drug candidates is central to the new drug discovery paradigm. Better to kill compounds before moving them into expensive clinical trials.  

big pharmas: MedAdNews publishes an annual list of the top 50 pharmaceutical companies each September. "Biotech" companies such as Amgen are bigger than some pharmas.

bioengineering:  The application of a systematic, quantitative, and integrative way of thinking about and approaching the solutions of problems important to biology, medical research, clinical proactive, and population studies. The NIH Bioengineering Consortium agreed on the following definition for bioengineering research on biology, medicine, behavior, or health recognizing that no definition could completely eliminate overlap with other research disciplines or preclude variations in interpretation by different individuals and organizations. Integrates physical, chemical, or mathematical sciences and engineering principles for the study of biology, medicine, behavior, or health. It advances fundamental concepts, creates knowledge for the molecular to the organ systems levels, and develops innovative biologics, materials, processes, implants, devices, and informatics approaches for the prevention, diagnosis, and treatment of disease, for patient rehabilitation, and for improving health. NIH, Office of External Research, Bioengineering Definition Committee, July 24, 1997  http://www.becon.nih.gov/bioengineering_definition.htm  

biogenerics:  So far, drugs based on large biological molecules have been immune from copycat competition since most are still patent- protected and, critically, regulators in major markets have yet to set clear rules for approving generic versions. But so- called "biogenerics" are gaining a foothold in Asia, where patents on original versions have expired or patent protection does not exist, and generics firms are looking hungrily at Europe as their next major outlet. [Ben Hirschler, Biotech drug copycats get ready to pounce, San Diego Union Tribune, Sept, 18, 2002]    
http://www.signonsandiego.com/news/business/biotech/ 20020918-0547-health-biotech-generics.html  Broader term: generic drugs  Related terms: follow ons, me toos

bioinformatics:  Roughly, bioinformatics describes any use of computers to handle biological information. In practice the definition used by most people is narrower; bioinformatics to them is a synonym for "computational molecular biology" - the use of computers to characterise the molecular components of living things. [Damian Counsell, bioinformatics.org FAQ] http://bioinformatics.org/faq/#whatIsBioinformatics See for tight and loose definitions of bioinformatics, and information on how long the term has been used. Research, development or application of computational tools and approaches for expanding the use of biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze, or visualize such data. Biomedical Information Science and Technology Initiative BISTI Bioinformatics at the NIH, 2000  http://www.bisti.nih.gov/ 

We have coined the term Bioinformatics for the study of informatic processes in biotic systems. Our Bioinformatic approach typically involves spatial, multi- leveled models with many interacting entities whose behavior is determined by local information. Theoretical Biology Group, Univ. of Utrecht, Netherlands, Paulien Hogeweg Director  http://www-binf.bio.uu.nl/

Original definition was “the study of informatic processes in biotic systems” Paulien Hogeweg MIRROR beyond MIRROR, puddles of LIFE, in

Alternatively computational biology

biologic product:  Any virus, serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries.  Biologic products are a subset of "drug products" distinguished by their manufacturing processes (biological process vs. chemical process). In general, the term "drugs" includes biologic products. US FDA glossary http://www.fda.gov/cder/drugsatfda/glossary.htm 

biological chemistry: A multi-disciplinary area with strong links to fundamental molecular and mechanistic topics. These topics are essential for the progress in the field. IUPAC shall be visible and shall have a central role in efforts to support strong links between chemistry and biology. ...Informal discussions at the Beijing GA resulted in a proposal to establish contacts with interested partners within IUPAC to form an informal discussion forum for the coordination and promotion of activities within the area of biological chemistry.  ...  The project will stimulate contacts and interactions between scientists who are active in the field. The aim of the project is to make an inventory and a feasibility study in order to present some proposals for IUPAC activities within this area.  IUPAC,  Chemistry for Biology - an inventory of interdivisional and interdisciplinary activities within IUPAC in the field of biological chemistry, 2006  http://www.iupac.org/projects/2005/2005-042-1-300.html 

biologics: Include blood, vaccines, tissue, allergenics and biological therapeutics. About CBER, Center for Biologics Evaluation and Research, FDA, US  http://www.fda.gov/cber/about.htm  

biological markers:   Measurable and quantifiable biological parameters (e.g. specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health - and physiology related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. MeSH, 1989 

 1. Parameter that can be used to identify a toxic effect in an individual organism and can be used in extrapolation between species. 2. Indicator signalling an event or condition in a biological system or sample and giving a measure of exposure, effect, or susceptibility.  [IUPAC Tox] 

Biological markers can reflect a variety of disease characteristics, including the level of exposure to an environmental or genetic trigger, an element of the disease process itself, an intermediate stage between exposure and disease onset, or an independent factor associated with the disease state but not causative of pathogenesis. Depending on the specific characteristic, biomarkers can be used to identify the risk of developing an illness (antecedent biomarkers), aid in identifying disease (diagnostic biomarkers), or predict future disease course, including response to therapy (prognostic biomarkers). Antecedent Biomarkers in Alzheimer's Disease, Alzheimers Research Forum, 2003  http://www.alzforum.org/res/enab/workshops/biomarkers.asp 

Alternatively/Related/synonymous? terms: biomarkers, genetic markers, surrogate markers; Broader term: markers  Narrower term: genomic biomarkers

biomathematics: The application of mathematics to problems in biology and medicine. An essential tool in fields such as population genetics, cellular neurobiology, comparative genetics, biomedical imaging, pharmacokinetics, and epidemiology. It plays an increasingly vital role in the effort to understand diseases and disorders, and to improve therapies.  Collection Development Manual, National Library of Medicine, US 2004  http://www.nlm.nih.gov/tsd/acquisitions/cdm/subjects14.html 

biomedical companies:  Relation[s] to SIC/ NAICs codes?

BioMEMS Biological MicroElectro Mechanical Systems: Includes micro & nano drug delivery, interface of nanoscience and tissue engineering, microfluidics, and miniaturized total analysis systems (microTAS), biosensors, innovations in mass spectrometry, and nanoscale imaging.  

biomimetics: An interdisciplinary field in materials science, ENGINEERING, and BIOLOGY, studying the use of biological principles for synthesis or fabrication of BIOMIMETIC MATERIALS. MeSH 2003

There is a need to develop the next generation of restorative materials and medical implants. New avenues of scientific inquiry may enable the development of biomaterials that are safe, reliable, "smart", long- lasting, and perform ideally in their respective biological environments. ... Over the last few years biomimetics and tissue engineering have emerged as a new vision in the field of tissue and organ repair and restoration. Biomimetics and tissue engineering are interdisciplinary fields that combine information from the study of biological structures and their functions with physics, mathematics, chemistry and engineering for the generation of new materials, tissues and organs. These approaches can offer new ways of: (a) developing biological solutions for future design and synthesis of composite materials such as bone, cartilage, tendon, ligament, skin, dentin, enamel, cementum and periodontal ligament; (b) replacing and assembling functional tissues and organs; and (c) evaluating medical and dental implants. In the area of craniofacial, oral and dental principles from biomimetics and tissue engineering are applied to developing dental and facial implants, new polymers for guided tissue regeneration used in treating periodontal disease and bone and connective tissue defects, coral- based hydroxyapatite replicas for reconstruction of alveolar ridges and other osseous defects, temporomandibular joint (TMJ) and other joint prostheses, formation of bone matrix substitutes, and artificial replicas of bone, skin, and mucosa.  [National Institute of Dental Research, NIH, US, Biomimetics and Tissue Engineering in the Restoration of Orofacial Tissues, RFA: DE-98-009, June 19, 1998] http://grants.nih.gov/grants/guide/rfa-files/RFA-DE-98-009.html

biomolecular materials: An emerging discipline, materials whose properties are abstracted from biology. They share many of the characteristics of biological materials but are not necessarily of biological origin. For example, they may be inorganic materials that are organized or processed in a biomimetic fashion. A key feature of biological and biomolecular materials is their ability to undergo self- assembly. Biomolecular self- assembling materials, National Academy of Sciences 1996  http://www.nas.edu/bpa/reports/bmm/bmm.html#PBMM

biomolecular screening:  Over the past 15 years, high throughput screening (HTS) of small molecules has become a mainstay in the drug discovery process both in lead discovery and lead optimization. In both HTS and routine screening to optimize lead structures, new technologies, techniques and terminology have emerged. A definitive glossary of biomolecular screening terms will be broadly useful to scientists involved in the drug discovery process. The glossary will be generated in collaboration with the Society for Biomolecular Screening. Update of 1999 glossary Glossary of terms used in biomolecular screening Chemistry and Human Health Division (VII) IUPAC project Number: 2004-019-3-700, last update March 2005 http://www.iupac.org/projects/2004/2004-019-3-700.html

biomolecules: An organic molecule, part of a living organism. Includes proteins, DNA, RNA

biomotors: Driven by energy sources such as adenosine triphosphate (ATP) for chemical transduction and other processes. These biomotors are considered to be biomolecular and are discussed in the body of this report, but strictly speaking they do not conform to the panel's definition of self- assembly. Biomolecular self- assembling materials, National Academy of Sciences 1996  http://www.nas.edu/bpa/reports/bmm/bmm.html#PBMM 

biopharmaceutical:  Any therapeutic biological compound, including recombinant proteins, monoclonal and polyclonal antibodies, antisense oligonucleotides, therapeutic genes, and recombinant and DNA vaccines. Tufts Center for the Study of  Drug Development, Glossary, 2004  http://csdd.tufts.edu/InfoServices/Glossary.asp 

biopolymers: Macromolecules (including proteins, nucleic acids and polysaccharides) formed by living organisms. [IUPAC Compendium]  Broader term: polymers

biorobotics:   Our research focuses on the role of sensing and mechanical design in motor control, in both robots and humans. This work draws upon diverse disciplines, including biomechanics, systems analysis, and neurophysiology. The main approach is experimental, although analysis and simulation play important parts.  In conjunction with industrial partners, we are developing applications of this research in biomedical instrumentation, teleoperated robots, and intelligent sensors. Harvard Biorobotics Laboratory, 2004.  http://biorobotics.harvard.edu/ 

borderline products:  Products which are close to the boundary between medicines, which need a licence, and others, such as nutritional supplements, cosmetics etc., which do not. Classification depends either on the ingredient or the claim or both. Medicines Control Agency, UK, Pilot publication scheme, Glossary of terms, 2003 http://www.mca.gov.uk/pilot/app1.htm#A  

brand name drug: A drug marketed under a proprietary, trademark- protected name. Glossary, Drugs@FDA, CDER, 2004 http://www.fda.gov/cder/drugsatfda/glossary.htm  Related terms: proprietary drug, proprietary name

biotechnology: The integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof  and molecular analogues for products and services. IUPAC Compendium 

biotechnology firms: The congressional Office of Technology concluded in its pathbreaking 1984 report, and emphasized even more strongly in another 1991 report, that "biotechnology" is not an industrial sector, but rather a set of methods useful in many industrial sectors (usually established ones such as drugs and biologics, devices, or agriculture), but also for some entirely new applications (e.g., DNA forensics). Many firms, almost 1500 listed by the various online services, are called "biotechnology" firms because they are largely built around technologies developed since 1980. These firms are generally competing in established markets, however, even when they compete by using novel products, services, and technical approaches. Robert Cooke- Deegan et. al., World Survey of Funding for Genomics Research: Final Report to the Global Forum for Health Research and the World Health Organization,  September 2000  http://www.stanford.edu/class/siw198q/websites/genomics/finalrpt.htm 

biotechnology industry:  The biotechnological innovations of the 1970’s took until the 1990’s to integrate.  "The Pharmaceutical Industry and the Revolution in Molecular Biology: Exploring the Interactions between Scientific, Institutional and Organizational Change, Iain M. Cockburn, Rebecca Henderson, Scott Stern, 1999. http://www.cid.harvard.edu/cidbiotech/events/henderson.htm   

Biotechnology started as a means for producing biopharmaceuticals.  It has only relatively recently begun to be fully integrated into the drug discovery and development process.

blockbuster drugs: Blockbuster drugs are defined as drugs with $1 billion or more in sales.  Mega- blockbusters are drugs with sales of $1 billion plus in their first year.  IMS Health, Market Insight, Mar. 19, 2002 http://www.ims-global.com/insight/news_story/0203/news_story_020317.htm

90% of drugs marketed by big pharma bring in less than $180 million per year. Compare that number to the total cost of $350- 600 million for approving a single drug (including all the failures that lead up to it). Of course, one might think that the money can be made back in four years, but drugs have a huge maintenance cost in terms of regulatory compliance, marketing and sales. The margin on a drug- to- drug basis is very slim. This places the onus on the other 10% of drugs to be blockbusters – to more than make up for most of the other drugs that are earning far too little revenue. This is how the industry has structured itself around a blockbuster mentality – a reliance on drugs that bring in at least $500 million per year in revenue. Considering the odds of achieving blockbuster status, this is a very high- risk strategy. Pharmaceutical companies will have to change their ways if they are going to enter the new era of individualized medicine. 

Related terms: FIPCO, franchises- pharmaceutical, market fragmentation, multibusters,  pharmaceutical industry

bottom up: The classical reductionist approach to biology which aims to examine the smallest units to gain insight into the larger ones. Mendelian genetics, which looks at single genes, is a bottom- up approach.   Compare top- down 

cancer genomics: With approximately 12 million new cases of cancer occurring worldwide each year, and 5-year survival rates for cancer patients no greater than 50%, improved therapies are clearly required. Up until the middle of the last decade, cancer therapeutics focused on cytotoxic agents identified using screening processes based on cancer cell lines. Although these products have been moderately successful, patients' response rates have yet been generally disappointing. Most products have been fraught with severely toxic side effects, limiting their dosage, and their effectiveness has ceased after only a few cycles of therapy. During the last decade, research dedicated to the discovery of new cancer products has concentrated on signaling pathways within cells associated with the growth, proliferation, apoptosis, and migration of cancer cells, and their eventual establishment into 

Technology is enabling ever increasingly rapid DNA analysis and, with that, the ability to establish personalized genome analysis. This has opened up the possibility of determining an individual's susceptibility to cancer at birth, and at selected periods during his or her life. In addition, the technology is enabling the identification of genetic components in cancer at the cellular and molecular levels - factors that will help identify new therapeutic targets and facilitate more effective selection of the drugs currently available on a patient- by- patient basis. CHI Cancer Genomics: Commercial Developments and Identification of New Molecular Targets for Therapy  report, 2003

cancer proteomics: The use of DNA microarrays to study cancer is as established as the technology itself [5, 6]. Transcriptome data is not only used to classify different types of cancer, but to shed light on known and unknown cancer genes: proto- oncogenes, oncogenes, and tumor suppressor genes. Proteome data, on the other hand, is not as pervasive, largely due to technological limitations. However, with the steady advancements in the tools mentioned above, “cancer proteomics” is becoming a reality. James Kuo "Proteomics and its applications to cancer research" Molecular Biology & Biochemistry, Yale Univ. 2000  http://bioinfo.mbb.yale.edu/mbb452a/2000/projects/James--Kuo.html

CBER Center for Biologics Evaluation and Research: Part of the US FDA. CBER is responsible for ensuring the safety of this nation's entire blood supply and the products derived from it; the production and approval of safe and effective childhood vaccines, including any future AIDS vaccines; the proper oversight of human tissue for transplantation; an adequate and safe supply of allergenic materials and anti- toxins; the safety and efficacy of biological therapeutics, including an exciting new array of biotechnology- derived products used to treat diseases such as cancer and AIDS. http://www.fda.gov/cber/index.html

CDER Center for Drug Evaluation and Research:  http://www.fda.gov/cder/  Part of the US FDA  Categories of Therapeutic Biological Products Transferred to CDER from CBER, June 30, 2003: Monoclonal antibodies for in-vivo use, Proteins intended for therapeutic use, including cytokines (e.g. interferons), enzymes (e.g. thrombolytics), and other novel proteins, except for those that are specifically assigned to CBER (e.g., vaccines and blood products). This category includes therapeutic proteins derived from plants, animals, or microorganisms, and recombinant versions of these products. Immunomodulators (non- vaccine and non- allergenic products intended to treat disease by inhibiting or modifying a pre- existing immune response). Growth factors, cytokines, and monoclonal antibodies intended to mobilize, stimulate, decrease or otherwise alter the production of hematopoietic cells in vivo ¹ Transfer of Therapeutic Products to the Center for Drug Evaluation and Research, CBER, FDA, US, 2004 http://www.fda.gov/cber/transfer/transfer.htm

cDNA complementary DNA: A single stranded DNA molecule with a nucleotide sequence that is complementary to an RNA molecule; cDNA is formed by the action of the enzyme reverse transcriptase on an RNA template. After conversion to the double stranded form, cDNA is used for molecular cloning or for hybridization studies. [IUPAC Biotech]

A complementary DNA for a messenger RNA molecule. Unlike an mRNA, a cDNA can be easily propagated and sequenced. [NCBI] 

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA- dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not cDNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe. MeSH, 1994

chaperome: The goal of the "All Chaperome" project is to characterize the molecular chaperones of C. elegans. We have identified approximately 170 chaperones corresponding to the major classes of chaperones and co-chaperones conserved in S. cerevisiae, and vertebrates.  Taking advantage of the lineage analysis of C. elegans, we are determining the expression pattern of each chaperone gene to establish a basis for network interactions and tissue specificity during development and aging.  Morimoto Laboratory, All Chaperome Project, 2007  http://www.biochem.northwestern.edu/ibis/morimoto/research/research_chap2.html Thanks to Heike Aßmus, University of Rostock for alerting me to this -ome. 

chemical genetics: A "chemistry first" approach to drug discovery. Chemical genetics strategies start with libraries of chemical compounds, and then screen these libraries to find compounds that produce differences in a disease- relevant phenotype. Once a phenotype modifying compound is found, it is used to identify the particular target protein to which it binds in the cells or small model organisms in which it had previously been studied.  Sometimes used interchangeably with "chemical genomics".  CHA, Cambridge Healthtech Advisors Model Animal Systems: Emerging Applications and Commercial Opportunities in Drug Discovery and Development, report, 2004

As the term has traditionally been used, has referred to studies that uncover the genetically controlled pathways influenced by a single specific compound. Also used to describe a method pioneered by Stuart Schreiber (Harvard Medical School, Howard Hughes Medical Institute involving a phenotypic screen employing a vast library of small molecules that have been introduced into a cellular assay. ...  The coverage of such studies can be genomic, but the detailed activity information they provide is at the genetic level (one gene within a particular pathway) http://www-schreiber.chem.harvard.edu  

"Chemical genetics approach" first coined [by Rebecca Ward, at Harvard University] on the inaugural cover of Chemistry and Biology nine years ago. Her term reminds us that to understand a life process you should perturb it and determine the consequence and that such an approach should strive to have the broad power and generality of  genetics. Stuart L. Schreiber, The Small Molecule Approach to Biology, Chemical & Engineering News, March 3, 2003 http://www-schreiber.chem.harvard.edu/home/pdffiles/8109genomics.pdf

Alternatively/Related terms: biochemical genomics, chemical genomics, chemogenomics, chemical proteomics

chemical information: Many people view chemoinformatics as an extension of chemical information, which is a well established concept covering many areas that employ chemical structures, data storage and computational methods, such as compound registration databases, on- line chemical literature, SAR analysis and molecule- property calculation. [Timothy Ritchie "Chemoinformatics; manipulating chemical information to facilitate decision- making in drug discovery" Drug Discovery Today 6(16): 813-814, Aug. 2001

chemical information system: Must include registration, computed and measured properties, chemical descriptors and inventory. The primary purpose is to be able to identify a chemical substance, find compounds similar to the target compound and determine the location of the compound. To effectively build it, an object definition of the chemical sample is paramount…The hub [central database] of the chemical information system is the inventory system. [Frank Brown "Chemoinformatics: What is it and How does it Impact Drug Discovery" Annual Reports in Medicinal Chemistry 33: 375-384, 1998]

cheminformatics: The practice of  finding the "best- fitting" compounds to address particular targets. The field encompasses diversity analysis and library design, virtual screening, rational drug design, and tools and approaches for predicting activity and other properties from structure. 

Going by the numbers in  Google.com cheminformatics seems to be the currently most used form of this word, overtaking chemoinformatics in about 2001.  

Alternatively chemical informatics, chemical information, chemi-informatics

chemoinformatics:  Chemoinformatics is an integral part of the discipline of knowledge management. [Nicholas J. Hrib, Norton P. Peet "Chemoinformatics: are we exploiting these new science?" Drug Discovery Today 5 (11): 483- 485, Nov. 2000]

Increasingly incorporates "compound registration into databases, including library enumeration; access to primary and secondary scientific literature; QSAR Quantitative Structure Activity Relationships) and similar tools for relating activity to structure; physical and chemical property calculations; chemical structure and property databases, chemical library design and analysis; structure- based design and statistical methods. Because these techniques have traditionally been considered the realms of scientists from different disciplines, differences in computer systems and terminology provide a barrier to effective communication. This is probably the single most challenging problem that chemoinformatics must solve. [M Hann and R Green "Chemoinformatics – a new name for an old problem?" Current Opinion in Chemical Biology 3:379- 383, 1999]

Mixing of information technology and management to transform data into information and information into knowledge for the intended purpose of making better decisions faster in the arena of drug lead identification and optimization. ..In Chemoinformatics there are really only two [primary] questions: 1.) what to test next and 2.) what to make next. The main processes within drug discovery are lead identification, where a lead is something that has activity in the low micromolar range, and lead optimization, which is the process of transforming a lead into a drug candidate. [Frank Brown  "Chemoinformatics: What is it and How does it Impact Drug Discovery" Annual Reports in Medicinal Chemistry 33: 375-384, 1998

chemotherapy: Treatment with anticancer drugs 
Synonyms: Drug treatment (drug therapy), medication therapy, pharmacotherapeutics, pharmacotherapy  Genetics Home Reference, National Library of Medicine, NIH http://ghr.nlm.nih.gov/ghr/glossary/chemotherapy 

Often refers to cancer treatments, but is also used more generally for drug therapy, particularly antimicrobial drugs..

clinical trials: Pharmacogenomics is a key tool for the design and interpretation of clinical trials. It contributes to a precise definition of a disease. It has the ability to correlate drug response to genetic markers and predict dose response and adverse events in some cases. It allows for representative subject populations within the clinical trial, and it allows for the stratification of patient populations. The potential benefits of that include reduction of drug development time due to the demonstration of efficacy in specific populations; the optimization of clinical utility by linking sub- types and efficacy; and reduction of time to market. Other potential benefits include the ability to differentiate between responder and non- responder populations, which may lead to a greater likelihood of reimbursement in the end.

clinical proteomics: Aims to discovery proteins with medical relevance said Alan Sachs, a director of R&D at Merck. Such discoveries can be defined broadly as those that identify a potential target for pharmaceutical development, a marker(s) for disease diagnosis or staging and risk assessment, both for medical and environmental studies. (Note that there is a difference between developing biological insight and identifying clinically important diagnostic and prognostic protein- based assays.) Defining the Mandate of Proteomics in the Post- Genomics Era, Board on International Scientific Organizations, National Academy of Sciences, 2002 http://www.nap.edu/books/NI000479/html/R1.html

clone:  A population of genetically identical  cells produced from a common ancestor. Sometimes also used to refer to a number of recombinant DNA molecules all carrying the same inserted sequence. IUPAC Medicinal Chemistry, IUPAC Compendium 

Clone was coined by Herbert J. Webber in 1903 for "a colony of organisms derived asexually from a single progenitor" and was quickly adopted by botanists and cell biologists. But the popular perception of cloning can be traced to Alvin Toffler's Future Shock (1970) and was quickly popularized (and extended to items such as computers). But Lee Silver, Professor of Molecular Biology and Public Affairs, Princeton Univ. concludes that "the scientific community has lost control over Webber's pleasant sounding little word. Cloning has a popular connotation that is impossible to dislodge. We must accept that democratic debate on cloning is bereft of any meaning. Science and Scientists would be better served by choosing other words to explain advances in developmental biotechnology to the public". L. Silver "What are clones? They're not what you think they are" Nature 412 (6842): 21, 5 July 2001

cloning:  Using specialized DNA technology (see cloning vector) to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. This process is used by researchers in the Human Genome Project, and is referred to as cloning DNA. The resulting cloned (copied) collections of  DNA molecules are called clone libraries. A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. A third type of cloning produces complete, genetically identical animals such as the famous  Scottish sheep, Dolly.  [DOE] 

The process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism. [NHGRI]

Rooting plant cuttings and having identical twins can also be considered types of cloning.

combination products: Include (1) A product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity;

(2) Two or more separate products packaged together in a single package or as a unit and comprised of drug and device products, device and biological products, or biological and drug products;

(3) A drug, device, or biological product packaged separately that according to its investigational plan or proposed labeling is intended for use only with an approved individually specified drug, device, or biological product where both are required to achieve the intended use, indication, or effect and where upon approval of the proposed product the labeling of the approved product would need to be changed, e.g., to reflect a change in intended use, dosage form, strength, route of administration, or significant change in dose; or

(4) Any investigational drug, device, or biological product packaged separately that according to its proposed labeling is for use only with another individually specified investigational drug, device, or biological product where both are required to achieve the intended use, indication, or effect. Definition of a Combination Product, FDA, Office of Combination Products, As defined in 21 CFR § 3.2(e) http://www.fda.gov/oc/combination/definition.html

combination therapies: Today, combination products range from drug-drug combinations to drug-device combinations, such as drug-eluting stents for coronary blockages, to drug-biological products, such as monoclonal antibodies combined with a chemotherapy agent for the treatment of cancer. Each product type offers significant solutions to many of the problems plaguing healthcare. Insight Pharma Reports, Combination Therapies: Benefits and Challenges in Drug, Device and Biologicals Development, 2005 http://www.insightpharmareports.com/reports/2005/56_Combination/overview.asp 

As ever more combination therapies are applied in various areas of medicine, there is a growing need for quantitative descriptions of combination effects. While most of the scientific community has agreed on a basic standard for synergy, there is no consensus on quantifying the degree to which a combination may deviate from synergy, and no predictive models are accepted to serve as benchmarks.  This project will convene a working group, involving leading experts on combination effects, to (1) endorse the synergy criterion recommended at a recent meeting in Finland, (2) adopt standard measures of combination effect to quantify deviations from synergy, and (3) explore predictive combination-effect models for multiply-inhibited biological interaction networks. Quantifying the Effects of Compound Combinations Chemistry International 25 (4) July-Aug. 2004, http://www.iupac.org/publications/ci/2004/2604/pp5_2003-059-1-700.html

combinatorial chemistry:  Using a combinatorial process to prepare sets of  compounds from sets of  building blocks. IUPAC Combinatorial Chemistry   Related terms: combinatorial libraries, diversity, microtiter plates, molecular diversity, fully combinatorial, pool/ split

companion diagnostics: One trend in genetic diagnostics and therapeutics is to become increasingly intertwined.  Companion diagnostics identify subsets of patients who would benefit from a specific drug. 

complex: It has become common to use complicated and complex interchangeably … The essence of ‘complicated’ is hard to figure out. ..Complex, on the other hand is a term reserved for systems that display properties that are not predictable from a complete description of their components, and that are generally considered to be qualitatively different from the sum of their parts. [Editorial, "Complicated is not complex" Nature Biotechnology 17: 511 June 1999] 

Would it be fair to say that Mendelian genetics is linear, while genomics and polygenic diseases/traits are nonlinear?

According to the Oxford English Dictionary one of the meanings of complicated is complex, though it also means not easy to unravel or separate. Both complex and complicated are contrasted with simple. Whatever the original senses of these two words, the above distinction seems a useful one now. 

Related term: complexity; 
Narrower terms: biocomplexity, complex diseases, complex genomes; complex phenotypes, complex traits  

complex diseases: Diseases characterized by risk to relatives of an affected individual which is greater than the incidence of the disorder in the population. [NHLBI] 

Are complex diseases essentially the same as polygenic diseases?

complex phenotypes: Those that exhibit familial clustering, which may mean that there is some genetic component, but that do not occur in Mendelian proportions in pedigrees. Complex phenotypes may be continuous in distribution, like height or blood pressure, or they may be dichotomous, like affected and not affected. The complexity arises from the fact one cannot accurately predict the expression of the phenotype from knowledge of the individual effects of individual factors considered alone, no matter how well understood each separate component may be. Genetic Architecture, Biological Variation and Complex Phenotypes, PA-02-110, May 29, 2002- June 5, 2005 http://grants1.nih.gov/grants/guide/pa-files/PA-02-110.html

complex trait: Has a genetic component that is not strictly Mendelian (dominant, recessive, or sex linked) and may involve the interaction of two or more genes to produce a phenotype, or may involve gene environment interactions." [NHLBI]  Related term: genetic architecture 

complexity:: Currently there are more than 30 different mathematical descriptions of complexity. However we have yet to understand the mathematical dependency relating the number of genes with organism complexity. [J. Craig Venter et. al. "The sequence of the Human Genome" Science 291 (5507): 1347, Feb. 16, 2001] 

An ill- defined term that means many things to many people. Complex things are neither random nor regular, but hover somewhere in between. Intuitively, complexity is a measure of  how interesting something is. Other types of complexity may be well defined. [Gary William Flake, Computational Beauty of Nature: Computer Explorations of Fractals, Chaos, Complex Systems, and Adaptation, MIT Press, 1998] http://mitpress.mit.edu/books/FLAOH/cbnhtml/glossary-C.html#complexity

Complexity resources http://www.comdig.org/ 

computer aided diagnosis CAD: A general term used for a variety of artificial intelligence techniques applied to medical images. CAD methods are being rapidly developed at several academic and industry sites, particularly for large-scale breast, lung, and colon cancer screening studies. X-ray imaging for breast, lung and colon cancer screening are good physical and clinical models for the development of CAD methods, related image database resources, and the development of common metrics and methods for evaluation. For large- scale screening applications CAD methods are an important for: (a) improving the sensitivity of cancer detection, (b) reducing observer variation in image interpretation, (c) increasing the efficiency of reading large image arrays, (d) improving efficiency of screening by identifying suspect lesions or identifying normal images, and (e) facilitating remote reading by experts (e.g., telemammography).

Image processing tools are also being developed for temporal analysis of serial images, with the aim of detecting early subtle changes that might not be obvious to the reading physician. Temporal analysis requires additional consensus on the development of reference standards (electronic ground truth), software modules for registration of serial images and related image segmentation. In addition, CAD techniques can improve the specificity of cancer detection by assigning a quantitative estimate of the probability that a detected lesion is benign or malignant. Another promising application of CAD is predicting which cases are most suitable for a particular treatment option. NEW NCI INITIATIVES IN COMPUTER AIDED DIAGNOSIS, Laurence P. Clarke, National Cancer Institute,  http://www3.cancer.gov/dip/spieppr.htm

computational physiology: The International Union of Physiological Sciences (IUPS) Physiome Project is an internationally collaborative open- source project to provide a public domain framework for computational physiology, including the development of modeling standards, computational tools and web-accessible databases of models of structure and function at all spatial scales [1,2,3]. It aims to develop an infrastructure for linking models of biological structure and function across multiple levels of spatial organization and multiple time scales. The levels of biological organisation, from genes to the whole organism, includes gene regulatory networks, protein- protein and protein- ligand interactions, protein pathways, integrative cell function, tissue and whole heart structure- function relations. The whole heart models include the spatial distribution of protein expression. Keynote: Peter J. Hunter, Univ of Auckland, International Society of Computational Biology, Detroit, MI, 2005 http://www.iscb.org/ismb2005/keynotes.html 

Copy Number Polymorphisms CNPs: Will become a valuable tool for defining relative phenotypes in a population. Insight Pharma Reports: Comparative Genomic Hybridization: Current State and Future Directions, 2006 

Copy-number polymorphisms (CNPs) represent a greatly underestimated aspect of human genetic variation. Recently, two landmark studies reported genome-wide analyses of CNPs in normal individuals and represent the beginning of an understanding of this type of large-scale variation.   Patrick G. Buckley^*, Kiran K. Mantripragada^*, Arkadiusz Piotrowski, Teresita Diaz de Ståhl and Jan P. Dumanski Copy-number polymorphisms: mining the tip of an iceberg, Trends in Genetics 21 (6): 315- 317, June 2005  http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCY-4G1PKNS-1&_user=10&_coverDate=06%2F30%2F2

Another term for CNV

copy number variation CNV: We defined a CNV as a DNA segment that is 1kb or larger and present at variable copy number in comparison with a reference genome. A CNV can be simple in structure, such as tandem duplication, or may involve complex gains or losses of homologus sequences at multiple sites in the genome. Richard Redon et. al, Global Variaiton in copy number in the human genome, Nature 2006 Nov 23;444 (7118): 444- 454   

Related terms: SNP, HapMap

data quality:  A vital consideration for data analysis and interpretation.  While people are still reeling from the vast amount of data becoming available, they need to brace themselves to both discard low quality data and handle much more at the same time.  

developability: Drug 'developability' assessment has become an increasingly important addition to traditional drug efficacy and toxicity evaluations, as pharmaceutical scientists strive to accelerate drug discovery and development processes in a time- and cost-effective manner. D. Sun et. al, In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. Curr Opin Drug Discov Devel.; 7(1): 75- 85, Jan 2004

diagnosis: Allen Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo SmithKline] notes that “precise diagnoses leading to universal specific treatments are, for many illnesses, myths... for many diseases there is no accurate, single diagnostic test” . [A.D. Roses “Pharmacogenetics and future drug development and delivery” Lancet 355 (9212):1358-61 Apr 15, 2000]   Narrower terms: companion diagnostics, molecular diagnostics

diseases: The human genome sequence will dramatically alter how we define, prevent, and treat disease. As more and more genetic variations among individuals are discovered, there will be a rush to label many of these variations as disease- associated. We need to define the term disease so that it incorporates our expanding genetic knowledge, taking into account the possible risks and adverse consequences associated with certain genetic variations, while acknowledging that a definition of disease cannot be based solely on one genetic abnormality. Disease is a fluid concept influenced by societal and cultural attitudes that change with time and in response to new scientific and medical discoveries. Historically, doctors defined a disease according to a cluster of symptoms. As their clinical descriptions became more sophisticated, they started to classify diseases into separate groups, and from this medical taxonomy came new insights into disease etiology. K Larissa et. al. "Defining Disease in the Genomics Era"  Science 293 (5531): 807- 808, Aug. 3, 2001  http://www.sciencemag.org/cgi/content/full/293/5531/807 

Collections of symptoms and signs (phenotypes) that appear to be similar … Similar clinical phenotypes may have very different underlying mechanisms. As genetic capabilities increase, we will have additional tools to subdivide disease designations that are clinically identical. [Allen D. Roses “Pharmacogenetics and future drug development and delivery” Lancet 355 (9212):1358- 1361 Apr 15, 2000

disruptive technologies: Some technologies are improved in a linear fashion or incrementally.  Others truly change the paradigm.   Clayton Christensen writes about these in The Innovator's Dilemma. What is particularly interesting about Christensen's analysis (based on data from the disk drive industry) is that he found disruptive technologies tended to be much cheaper than existing technologies. Existing companies were quite capable of developing the technologies (and had). What they couldn't do was figure out how to market them and whether it made sense to devote sufficient resources to them (which in many cases would not have been the responsible thing to do.)  

The pharmaceutical industry is mentioned only in passing, but the success of larger established companies either partnering with smaller less established ones (clearly happening in the pharmaceutical and biotechnology sectors) or spin- off of promising developments as separate companies (Johnson & Johnson said to be particularly good at this) makes a lot of sense.

Related term: nonlinear.

DNA vaccines: DNA- mediated immunization, colloquially known as DNA vaccines. This represents a radical change in the way that antigens are delivered; it involves the direct introduction of a plasmid DNA encoding an antigenic protein which is then expressed within cells of the organism. This leads to surprisingly strong immune responses, involving both the humoral and cellular arms of the immune system.  Robert G. Whelan, DNA Vaccines, Cyberspace and Self Help Programs, Intervirology 39: 120-125 (1996) DNAvaccine. com http://dnavaccine.com/

drug: Any substance which when absorbed into a living organism may modify one or more of its functions. The term is generally accepted for a substance taken for a therapeutic purpose, but is also commonly used for abused substances. Synonymous with medicine, pharmaceutical.  [IUPAC Compendium]  

A substance recognized by an official pharmacopoeia or formulary, a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. A substance (other than food) intended to affect the structure or any function of the body. A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device. Biologic products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process vs. biological process.) CDER, FDA Glossary http://www.fda.gov/cder/drugsatfda/glossary.htm 

Narrower terms: specialty pharmaceuticals. Compare biologics. 

drug development - costs:  The fully capitalized cost to develop a new drug, including studies conducted after receiving regulatory approval, averages $897 million, according to an analysis by the Tufts Center for the Study of Drug Development.  The announcement expands on the $802 million estimate released by the Tufts Center in November 2001, by including post-approval R&D costs. The $802 million figure includes total average preclinical and clinical costs up to the time of receiving FDA marketing approval. Estimates are in year 2000 dollars. Joseph DiMasi et. al, Tufts CSDD,  May 13, 2003  http://csdd.tufts.edu/NewsEvents/RecentNews.asp?newsid=29

drug discovery:  For any given target, HTS High Throughput Synthesis remains the predominant tool for identifying leads for further drug development. Those companies that can effectively deal with the flood of large numbers of potential targets coming out of genomics are those that can gain a significant competitive advantage. However, this abundance of new targets is both an opportunity and a threat. When companies are able to prioritize and validate targets, it allows them to narrow the focus to those leads offering improved chances of success.

Related terms: target validation

drug interactions: Examples of drug interaction terms include adverse drug interaction, drug- drug interaction, drug- laboratory interaction, drug- food interaction, etc. Drug interaction is defined as, "An action of a drug on the effectiveness or toxicity of another drug". .. Due to non- uniform usage of these terms, it is sometimes difficult to compare various studies and derive incidence rates, etc. for ADRs, and Drug Interactions   [Saeed A Khan, "Drug Interaction or Adverse Drug Reaction? Confusing Terms", British Medical Journal 10 July, 1998] http://bmj.com/cgi/eletters/316/7149/1930

drug safety: CDER [FDA] evaluates the safety profiles of drugs available to American consumers using a variety of tools and disciplines throughout the life cycle of the drugs. We maintain a system of postmarketing surveillance and risk assessment programs to identify adverse events that did not appear during the drug development process. We learn about adverse events through required reporting by companies and through voluntary reports submitted to FDA’s MedWatch program, which together total more than 250,000 reports per year. Staff in the Office of Drug Safety use this information to identify drug safety concerns and recommend actions to improve product safety and protect the public health. Activities include updating drug labeling, providing more information to the community, implementing or revising a risk management program, and, on rare occasions, reevaluating approval or marketing decisions. Office of Drug Safety, CDER, FDA http://www.fda.gov/cder/Offices/ODS/default.htm

Drug Safety Initiative, FDA http://www.fda.gov/cder/drugSafety.htm

druggable:   Able to be modulated by a small molecule to produce a desired phenotypic change in cell targets.  

Variant spelling is drugable, but druggable is more common.

Alternatively/ Related terms: developability, drug-like, drug likeness, druggable, low hanging fruit, pharmaceutically tractable, privileged structure

DTC direct to consumer: Public Meeting Sept. 2003 presentations http://www.fda.gov/cder/ddmac/DTCmeeting2003_presentations.html 

efficacy:  Describes the relative intensity with which agonists vary in the response they produce even when they occupy the same number of receptors and with the same affinity. Efficacy is not synonymous to intrinsic activity. The property that enables drugs to produce responses. 

It is convenient to differentiate the properties of drugs into two groups, those which cause them to associate with the receptors (affinity) and those that produce stimulus (Efficacy). This term is often used to characterize the level of maximal responses induced by agonists. In fact, not all agonists of a receptor are capable of inducing identical levels of maximal responses. Maximal response depends on the efficiency of receptor coupling, i.e., from the cascade of events, which, from the binding of the drug to the receptor, leads to the observed biological effect. [IUPAC Medicinal Chemistry]

enabling technologies: The Human Genome Project taught that evolutionary improvement in existing technologies (e.g., DNA sequencing) can have a revolutionary impact on science. The systems approach taken by the Genomes to Life program dictates that existing technologies must evolve to a high-throughput capability. In addition, revolutionary technologies need to be developed, incorporating new modes of robotics and automation as well as advanced information and computing technologies. Enabling Technologies, DOE Genomes to Life, US http://www.doegenomestolife.org/technology/index.html

Frequently cited examples of enabling technologies for drug discovery and development are combinatorial chemistry, high-throughput screening, microarrays, bioinformatics and computational biology, nanotechnologies, and imaging (including biosensors and biomarkers

ethical drugs: The old term ethical drugs signified drugs advertised only to doctors. The expression refers to the original 1847 code of ethics of the AMA, which deemed advertising directly to the public to be unethical. Over time, the term came to mean legal drugs. FDAReview.org, Independent Institute, 2003 http://www.fdareview.org/glossary.shtml#ethical 

expression: The cellular production of the protein encoded by a particular gene.  The process includes transcription of DNA, processing of the resulting mRNA product and its translation into an active protein.  N.B. A recombinant gene inserted into a host cell by means of a vector is said to be expressed if the synthesis of the encoded polypeptide can be demonstrated.  IUPAC Bioinorganic, IUPAC Compendium

A description as to how a gene demonstrates a phenotype.  This can range from production of a mRNA to a disease.  If a disease gene carrier shows signs of the disease gene, then that gene is expressed.  Note that an individual must carry the disease gene and be penetrant  for it before the term expression is utilized. [NHLBI]  

Narrower terms: gene expression, protein expression. Related terms: expression profiling, molecular profiling

expression profiling:  Expression profiling is driving the pharmaceutical R&D process. It is being used downstream of target identification, as a biological readout for target modulation. Targets first identified through genomics then need to go through validation testing, to see if a phenotypic change occurs when a target is dysregulated. These targets or pathways can be modified by using either RNAi, or the use of a chemical ligand that interacts with a target. The results are compared in order to understand a compound’s activity for on- and off- target effects. 

Refers to the expression values for a single gene across many experimental conditions, or for many genes under a single condition. In the terminology of cluster format, the first case amounts to looking at a row of the data table, and the second case a column. 

fail fast: A term that has tended to make people in drug discovery and development wince, but considering the costs of later failures, it looks more and more like an attractive option.

fast followers:  Not just "me too drugs. 

fast track: The fast track process was established in the FDA Modernization Act of 1997. Under this act, NDAs are deemed either "standard" or "priority" (fast track). With the "standard" designation, the FDA’s goal is to complete the review and make a decision on the NDA within ten months after it has been filed. With the "priority" designation, used for drugs that address unmet medical needs, the target date is six months after the filing. However, actual approval times are typically longer. In certain cases, the FDA also offers "accelerated approval" to allow the marketing of drugs for life-threatening diseases, before the benefits to patients are formally demonstrated. This approval is made on the basis of a surrogate marker (e.g., a drug’s effect on survival).

FIPCO Fully Integrated Pharmaceutical Company:  Not as popular a goal in the 21st century as in the mid-late 1990's. 

franchises - pharmaceutical: In the pharmaceutical industry, we tend to think of franchises as a suite of relevant drugs marketed to a specific cluster of physicians. While this definition served our needs for sales efficiency and scientific credibility, it has left too much value on the table. We encourage the industry to re-think the idea of franchise in terms of brand identity, of the images, values and ideas consumers and other stakeholders, such as pharmacists, associate with a given brand. Vimal Bahuguna and Bob Lieberman, "From Patents to Franchises, Bogart Delafield Ferrier, US http://www.bdf.com/patentstofranchises.htm

function:   The vagueness of the term 'function' when applied to genes or proteins emerged as a particular problem, as this term is colloquially used to describe biochemical activities, biological goals and cellular structure. [Gene Ontology Consortium "Gene Ontology: tool for the unification of biology Nature Genetics 25: 25-29 May 2000] 

The term "function" means many things, and its meaning changes depending on who is asking the question and what sorts of experiments are being employed to probe it. Genomics by itself cannot usually determine even the biochemical, much less the cellular or physiological functions of a protein. Structural biology can determine the shape of the protein but cannot reliably determine its function; the coupling between overall structure and function is a loose one. Given a structure, one cannot determine where on the surface of a protein the likely binding sites for ligands are located and what those ligands are likely to be. Genomewide experiments have many false positives and false negatives and often do not distinguish indirect effects from direct ones. The consequences of the expression of a given gene sequence can only be determined by integrating the results from many different types of experiments, and the best way to carry out this integration is not obvious. "From Sequence to Consequence: The Problem of Determining the Functions of Gene Products in the Age of Genomics" Dr. Gregory A. Petsko, Brandeis Univ.  Chemogenomics/ Chemical Genomics Nov. 18- 19, 2002, Boston MA

Narrower terms: gene function, protein function

functional genomics:  Functional genomics aims to discover the biological function of particular genes and to uncover how sets of genes and their products work together in health and disease. In its broadest definition, functional genomics encompasses many traditional molecular genetic and other biological approaches. The development and application of global (genome- wide or system- wide) experimental approaches to assess gene function by making use of the information and reagents provided by structural genomics [in the original more limited sense of construction of high- resolution genetic, physical and transcript maps of an organism]. It is characterized by high throughput or large- scale experimental methodologies combined with statistical and computational analysis of the results. The fundamental strategy is to expand the scope of biological investigation from studying single genes or proteins to studying all genes or proteins at once in a systematic fashion. Phil Hieter and Mark Boguski "Functional Genomics: It's All How You Read It" Science 278: 601- 602, October 24, 1997

functional proteomics:  Is yielding large databases of interacting proteins and extensive pathways maps of these interactions are being scored and deciphered by novel high throughput technologies. However, traditional methods of screening have not been very successful in identifying protein- protein interaction inhibitor

gene (cistron): Structurally, a basic unit of hereditary material; an ordered sequence of nucleotide bases that encodes one polypeptide chain (via mRNA). The gene includes, however, regions preceding and following the coding region (leader and trailer) as well as (in eukaryotes) intervening sequences (introns) between individual coding segments (exons). Functionally, the gene is defined by the cis- trans test that determines whether independent mutations of the same phenotype occur within a single gene or in several genes involved in the same function. [IUPAC Compendium]

There are many discussions between biologists to find a comprehensive definition of a gene, which is not easy, if possible at all. For our purposes a gene is a continuous stretch of a genomic DNA molecule, from which a complex molecular machinery can read information (encoded as a string of A, T, G, and C) and make a particular type of a protein or a few different proteins. [Alvis Brazma, et. al., A quick introduction to elements of biology: 3.3 Genes and protein synthesis, European Bioinformatics Institute, Draft, 2001]  http://www.ebi.ac.uk/microarray/biology_intro.html#Genomes

Specific sequences of nucleotides along a molecule of DNA (or, in the case of some viruses, RNA) which represent the functional units of heredity. The majority of eukaryotic genes contain coding regions (codons) that are interrupted by non- coding regions (introns) and are therefore labeled split genes. [MeSH, 1965]

A gene is a DNA segment that contributes to phenotype/ function. In the absence of demonstrated function a gene may be characterized by sequence, transcription or homology. [HUGO, J.A. White et. al. Guidelines for Human Gene Nomenclature HGNC Human Genome Nomenclature Committee, 1997] http://www.gene.ucl.ac.uk/nomenclature/guidelines.html#2.2

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein [NHGRI] 

This definition doesn't specify that it applies only to humans - but by specifying "parents" it seems to rule out non- animal genes, and almost implies mammals, or at least warm- blooded organisms.

gene disruption: A key methodology in high- throughput gene functional analysis. Involves developing various methods for systematically disrupting genes throughout the genome of a model organism (resulting in knockouts, or null mutations of these genes) and then the phenotype (if any) of the mutant organism.

gene expression: The process by which a gene’s coded information is converted into the structures present and operating in the cell.  Expressed genes include those that are transcribed into mRNA and then translated into protein and those that are transcribed into RNA but not translated into protein (e.g. transfer [tRNA] and ribosomal [rRNA] RNAs). [DOE] 

The phenotypic manifestation of a gene or genes by the processes of gene action. [MeSH, 1990]

Our modern concept of gene expression dates back to 1961 when messenger RNA was discovered, the genetic code was deciphered, and the theory of genetic  regulation of protein synthesis was described. [O Ermolaeva et al “Data Management and analysis for gene expression arrays” Nature Genetics 20: 19- 23,1998]

The transcription of a gene and its processing to yield a mature messenger RNA (mRNA). (Note that in proteomic studies, the same term also includes the translation of the mRNA to produce a functional protein.) In studies of differential gene expression, one looks for genes whose expression levels differ significantly under different experimental conditions, for example in normal versus diseased states or in untreated versus treated subjects. This application is perhaps the most obvious use of microarrays.

Broader terms: expression, genome expression  Related term: protein expression

gene expression profiling: The determination of the pattern of genes expressed i.e., transcribed, under specific circumstances or in a specific cell. MeSH, 2000

gene manipulation: The use of in vitro techniques to produce DNA molecules containing novel combinations of genes or altered sequences, and the insertion of these into vectors that can be used for their incorporation into host organisms or cells in which they are capable of continued propagation of the modified genes. [IUPAC Biotech] 

gene patents: Much of the controversy surrounding patenting genes stems from a misunderstanding of the limitations of patent law. Numerous media sources often refer to "gene patents." This term is imprecise and can lead to the belief that it is possible to file for a blanket patent covering all the possible uses of a gene, or even a patent on the sequence itself. Further misunderstandings arise from the failure to differentiate between a patent that is pending and a patent that has been granted. .. [Patenting Genes, about.com] http://biotech.about.com/library/weekly/aa060900a.htm

The controversy over gene patents emerged when Dr. Craig Venter, CEO of Celera Genomics, sent 20,000 gene sequences to the PTO, claiming patents to the sequences and to procedures that would be used to diagnose disorders with the genes. The PTO denied these applications, suggesting that simply finding DNA sequences and claiming their use as a research reagent was not sufficient for a patent. The PTO thus indicated that it required the inventor of a gene to show a level of utility beyond the gene’s use as a research tool. ¶ 6 The standard of utility wielded by the PTO, however, has been far from clear. [THE FATE OF GENE PATENTS UNDER THE  NEW UTILITY GUIDELINES, Feb.  28 , 2001, Duke Law and Technology Review, Cite as 2001 Duke L. & Tech. Rev. 0008] http://www.law.duke.edu/journals/dltr/ARTICLES/2001dltr0008.html   Narrower terms: cDNA patents, disease gene patents, EST patents, gene fragments, SNP patents

Beginner's guide to gene patents, Guardian, UK, 2000 http://www.guardian.co.uk/genes/article/0,2763,397385,00.html

gene silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. MeSH 2000 Narrower term: RNAi RNA interference

gene therapy:  Encompasses at least four types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year [1986]. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. W. French Anderson "Human gene therapy: scientific and ethical considerations" J Med Philosophy 10 (3): 275- 291, Aug. 1985  Gene Therapy resources, Oak Ridge National Lab http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml  

genes, human:  At the 2000 Cold Spring Harbor Genome conference [May 10-14] "one of the hotly debated topics was the number of human genes. This has been estimated at anything from 35,000 to 150,000. Considering the spread of opinion, the only way to resolve was to get people to bet on it … This led to an interesting debate on the definition of a gene … and how to assess that number. A gene is a set of connected transcripts. A transcript is a set of exons via transcription followed (optionally) by pre- mRNA splicing. Two transcripts are connected if they share at least part of one exon in the genomic coordinates. At least one transcript must be expressed outside of the nucleus and one transcript must encode a protein. "Genesweep" Ensembl, European Bioinformatics Institute, UK http://www.ensembl.org/Genesweep/  

With the publication of the Human Genome Project draft sequence in Feb. 2001 we learned that the number of genes (about 30,000) seems to be many fewer than expected, but the number of proteins per gene, with alternative splicing (two to three, instead of one) is greater.  More surprises seem sure to be in store

genetic engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. MeSH, 1989  Related term: recombinant DNA technology

genetic enhancement: The use of genetic methodologies to improve functional capacities of an organism rather than to treat disease.  MeSH, 2002

The subject of much discussion and concern over the ethics of, though new disease diagnoses, treatments (and concepts of "disease") are much closer than true genetic enhancements. The popular conception of selective breeding focuses on optimization of one or a very few traits (which produces tomatoes which ship well but have no taste, and purebred dogs with congenital hip dysplasia. Little attention has been paid to the tradeoffs (predictable and not) inevitable among polygenic traits. 

"Regression to the mean" also factors in. While two tall or two bright people tend to have children who are taller or brighter than average, they are NOT usually taller or brighter than the parents are. Only microbes with their greatly enhanced opportunities for evolving (with such short reproductive spans) seem to quickly get reliably bigger, better (in a sense) and stronger. Biological homeostasis is incredibly powerful. We may never be able to "enhance" complex traits such as intelligence or strength.  But we need to learn how to talk about these issues -- preferably before actually being able to actually implement genetic enhancement.

Beyond therapy: (enhancement), US President's Council on Bioethics http://www.bioethics.gov/topics/beyond_index.html

genetic maps: The value of the genetic map is that an inherited disease can be located on the map by  following the inheritance of a DNA marker present in affected individuals (but absent in unaffected individuals), even though the molecular basis of the disease may not yet be understood nor the responsible gene identified. Genetic maps have been used to find the exact chromosomal location of several important disease genes, including cystic fibrosis, sickle cell disease, Tay- Sachs disease, fragile X syndrome, and myotonic dystrophy.  Primer on Molecular Genetics, Oak Ridge National Lab, US http://www.ornl.gov/hgmis/publicat/primer/prim2.html#1

Can be cytogenetic, linkage, or physical maps. Starting genetic maps is easier than finishing them.

genetic testing: Allen Roses, worldwide director of genetics for Glaxo Wellcome [now Glaxo SmithKline] notes  "Until now, government sponsored committees convened to address ‘genetic testing’ have generally limited their definition and their reports to concerns regarding diseases caused by single gene mutations … Another class of  'genetic tests’ is related to pharmacogenetics, including ... variants or other inherited polymorphic traits that are not diagnostic of disease … Clear language and differentiation of respective ethical, legal and societal issues are required to prevent inaccurate vernacular usage creating a confused public perception. Allen Roses, Pharmacogenetics and the practice of medicine” Nature 405: 857- 865, 15 June 2000   

genome: The complete set of chromosomal and extrachromosomal genes of an organism, a cell, an organelle or a virus; the complete DNA component of an organism. [IUPAC Biotech]

The fundamental concepts of genome, genotype and phenotype are not defined in a satisfactory manner within the biological literature. Not only are there inconsistencies in usage between various authors, but even individual authors do not use these concepts in a consistent manner within their own writings. We have found at least five different notions of genome, seven of genotype, and five of phenotype current in the literature. Our goal is to clarify this situation by (a) defining clearly and precisely the notions of genetic complement, genome, genotype, phenetic complement, and phenotype; (b) examining that of phenome; and (c) analysing the logical structure of this family of concepts. [M. Mahner, M. Kary "What exactly are genomes, genotypes and phenotypes? And what about phenomes?" Journal of  Theoretical Biology 186 (1): 55- 63, May 1997]

All the DNA contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria. [NHGRI] Size expressed by the number of base pairs. [DOE].

First used by H. Winkler in 1920, was created by elision of the words GENes and chromosOMEs, and that is what the term signifies: the complete set of chromosomes and their genes. [V McKusick "Genomics: Structural and Functional studies of genomes" Genomics 45:244-249 Oct. 15 1997]  

genomic DNA gDNA: The entire length of DNA, including non coding regions. (Sometimes called gDNA.) CHI Bioinformatics report  DNA which includes exons and introns, coding and noncoding regions. Compare with cDNA

genomics: Generation of information about living things by systematic approaches that can be performed on an industrial scale. Roger Brent "Genomic biology" Cell 100: 169-183 Jan 2, 2000 

The systematic study of the complete DNA sequences (GENOME) of organisms. MeSH, 2001

genotype: The genetic constitution of an organism as revealed by genetic or molecular analysis, i.e. the complete set of genes, both dominant and recessive, possessed by a particular cell or organism. [IUPAC Biotech]

The observed alleles at a genetic locus for an individual. [NHLBI] 

An organism’s genetic makeup, as revealed through molecular analysis.

genotyping: The process of assessing genetic variation present in an individual. CHA Cambridge Healthtech Advisors, Clinical Genomics: The Impact of Genomics on Clinical Trials and Medical Practice report, 2004

Used for diagnosis, drug efficacy, and toxicity. Utilizes genomic DNA that, after digestion, reacts with a SNP array to obtain an individual SNP pattern. These variations can for instance provide information about the diagnosis of a certain disease, or the effectiveness or side effect of a certain drug.  May refer to identifying one or more, up to the entire gene sequence of an organism. Compare phenotype Genotyping implies (though I haven't found this in print) determining known variants, as opposed to discovery of new ones.

Full DNA sequencing is the "gold standard" for genotyping. 

glycomics: The cascade of genetic information does not terminate with proteins but with glycans … diverse glycan structures are significantly related to various biological phenomena … glycans have potential to exhibit structural diversity, whose complexity is far greater than that of nucleic acids or proteins … Unless we adopt a global strategy involving the genome, proteome and glycome, we will never achieve an understanding of the glyco- code, which is probably based on a completely different system from those governing nucleic acids and proteins. J. Hirabayashi, J and K. Kasai “Glycomics, Coming of Age! Trends in Glycosciences and Glycobiology 12  (63): 1-5 Jan 2000]  http://www.gak.co.jp/TIGG/63PDF/GF.pdf 

Glycomics, one of the newest additions to the ‘omics’ family has recently experienced a huge surge of interest in the biopharmaceutical industry. The recognition of the important role glycosylation is playing in biological functions has led to a significant increase in biopharmaceutical companies who focus their research on carbohydrate - based drug development. Advanced technologies in analysis and synthesis result in better data about glycan structures, binding specifities and also on carbohydrate related genes. In addition, the number of carbohydrate related human diseases discovered is steadily increasing. New drugs are being developed in areas such as cancer treatment, angiogenesis, and vaccines. 

Alternatively: saccharomics  Related terms: carbohydrates glycobiology, glycoproteomics, glycosciences, glycotechnology

granularity: Essentially the level of detail. 

Concept of granularity, ISWorld Mailing List, Michael Chilton, 2001 http://www.isworld.org/isworldarchives/research.asp#  

HapMap: See International HapMap Project

haplotypes:  The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the MAJOR HISTOCOMPATIBILITY COMPLEX. MeSH 1987

haplotyping: Somatic cells, as opposed to germ cells, have two copies of each chromosome. A given single- base position may be homozygous for the wild- type base (each chromosome has the normal allele), homozygous for a SNP base (each chromosome has the altered allele), or heterozygous for two different bases (one chromosome has the normal allele and the other has the abnormal allele).

Haplotyping involves grouping subjects by haplotypes, or particular patterns of sequential SNPs, found on a single chromosome. These SNPs tend to be inherited together over time and can serve as disease- gene markers. The examination of single chromosome sets (haploid sets), as opposed to the usual chromosome pairings (diploid sets), is important because mutations in one copy of a chromosome pair can be masked by normal sequences present on the other copy.  Genes tend to travel in packs. This is good news for pharmacogenomics.

Broader terms genotyping, sequencing

high-content screening HTS: By using multiple fluorescent reporter systems, combined with high- resolution imaging and high- throughput image analysis, researchers can observe multiple intracellular events in individual cells. High- content screening (HCS) enables functional analysis of target and pathway modulation in living cells by potential drug compounds. Availability of high- content cellular information at early stages in drug discovery process will improve the quality of targets, hits, and leads; reduce late- stage attrition; and shorten time and cost of drug development.

high tech industry: The traditional perception of high tech - still reflected in our indicators - has been research- intensive manufacturing industries, like computers and aircraft. The penetration of technologies like information technology, biotechnology, and advanced materials throughout the economy