Designer Genes Designer Drugs A Funny Thing Happened

Designer Genes, Designer Drugs: A Funny Thing Happened on the Way to the Forum Fred Stoss Science and Engineering Information Center SUNY University at Buffalo Upstate New York Science Librarians Annual Meeting Cornell University October 23, 2013

A FUNNY THING HAPPENED ON THE WAY TO THE FORUM • Bull. Med. Libr. Assoc. 59 (4) Oct. 1971 – June 2, 1971 – New York City – Annual Meeting Program Committee experimented – 9 different forums presented simultaneously – Repeated in afternoon – “A funny thing happened on the way to the Forum. . We communicated. ” http: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 197657/pdf/mlab 00157 -0086. pdf

“Traditional Biology”

Physiology: Membrane Transport “New”

Biochemistry “New”

Forensics

High School Interests to College Enrolment in Forensics • CSI: Crime Scene Investigation – Pace University • Added undergraduate and grad-school degree programs – Purdue University • Introduction to Forensic Science Elective – Virginia Commonwealth University • Forensics majors from 114 to 220 – American Academy of Forensic Sciences • fields about 25 inquiries per week from people contemplating forensic careers – five times more than in 2002/2003

Evolution of the “New Biology” “Old School” Biology & Life Sciences Physics Chemistry Biochemistry & Medicine Polymer Physics Medicinal Chemistry & Pharmacy Science Genetics DNA/RNA Structure & Folding Combinatorial Chemistry Cell Biology & Physiology Instrumentation New: “Molecular & Structural Biology/Genetics, Genomics, Engineering New Pharmacogenomics, Toxicogenomics, Proteomics NEWEST: Informational Molecular Biology, NEWEST Computational Biology, Systems Biology Chemical Biology, Translational Medicine, Metablonics, Metabolonics, Microbiome, Translational Medicine, Clinical Genomics, Exposome, Array Analysis Bioinformatics Visualization Biotechnology Robotics Laboratory Automation Mathematics & Statistics Computer Science Topology & Knot Theory Hardware & Software Algorithmic Theory Information Science Gene Mapping, Micro Simulations and Modeling

Evolution of the “New Biology” “Old School” Biology & Life Sciences Physics Chemistry Biochemistry & Medicine Polymer Physics Medicinal Chemistry & Pharmacy Science Genetics DNA/RNA Structure & Folding Combinatorial Chemistry Cell Biology & Physiology Instrumentation New: “Molecular & Structural Biology/Genetics, Genomics, Engineering New Pharmacogenomics, Toxicogenomics, Proteomics NEWEST: Informational Molecular Biology, NEWEST Computational Biology, Systems Biology Chemical Biology, Translational Medicine, Metablonics, Metabolonics, Microbiome, Translational Medicine, Clinical Genomics, Exposome, Array Analysis Visualization Bioinformatics Biotechnology Robotics Laboratory Automation Mathematics & Statistics Computer Science Topology & Knot Theory Hardware & Software Algorithmic Theory Information Science Gene Mapping, Micro Simulations and Modeling Data Management

Evolution of the “New Biology” “Old School” Biology & Life Sciences Physics Chemistry Biochemistry & Medicine Polymer Physics Medicinal Chemistry & Pharmacy Science Genetics DNA/RNA Structure & Folding Combinatorial Chemistry Cell Biology & Physiology Instrumentation New: “Molecular & Structural Biology/Genetics, Genomics, Engineering New Pharmacogenomics, Toxicogenomics, Proteomics NEWEST: Informational Molecular Biology, NEWEST Computational Biology, Systems Biology Chemical Biology, Translational Medicine, Metablonics, Metabolonics, Microbiome, Translational Medicine, Clinical Genomics, Exposome, Array Analysis Visualization Bioinformatics Biotechnology Robotics Laboratory Automation Mathematics & Statistics Computer Science Topology & Knot Theory Hardware & Software Algorithmic Theory Information Science Gene Mapping, Micro Simulations and Modeling Data Management

Evolution of the “New Biology” “Old School” Biology & Life Sciences Physics Chemistry Biochemistry & Medicine Polymer Physics Medicinal Chemistry & Pharmacy Science Genetics DNA/RNA Structure & Folding Combinatorial Chemistry Cell Biology & Physiology Instrumentation New: “Molecular & Structural Biology/Genetics, Genomics, Engineering New Pharmacogenomics, Toxicogenomics, Proteomics NEWEST: Informational Molecular Biology, NEWEST Computational Biology, Systems Biology Chemical Biology, Translational Medicine, Metablonics, Metabolonics, Microbiome, Translational Medicine, Clinical Genomics, Exposome, Array Analysis Visualization Bioinformatics Biotechnology Robotics Laboratory Automation Mathematics & Statistics Computer Science Topology & Knot Theory Hardware & Software Algorithmic Theory Information Science Gene Mapping, Micro Simulations and Modeling Data Management

Evolution of the “New Biology” “Old School” Biology & Life Sciences Physics Chemistry Biochemistry & Medicine Polymer Physics Medicinal Chemistry & Pharmacy Science Genetics DNA/RNA Structure & Folding Combinatorial Chemistry Cell Biology & Physiology Instrumentation New: “Molecular & Structural Biology/Genetics, Genomics, Engineering New Pharmacogenomics, Toxicogenomics, Proteomics NEWEST: Informational Molecular Biology, NEWEST Computational Biology, Systems Biology Chemical Biology, Translational Medicine, Metablonics, Metabolonics, Microbiome, Translational Medicine, Clinical Genomics, Exposome, Array Analysis Visualization Bioinformatics Biotechnology Robotics Laboratory Automation Mathematics & Statistics Computer Science Topology & Knot Theory Hardware & Software Algorithmic Theory Information Science Gene Mapping, Micro Simulations and Modeling Data Management

Biology Abstracting & Indexing Services – Pharmaceutisches Central-Blatt – Engineering Index – Index Medicus 1830 1884 1879 • MEDLINE (1965) & Pub. Med (1996) – Science Abstracts 1898 – Chemical Abstracts (Sci. Finder Scholar) 1907 – Biological and Agricultural Index 1916/18 – Biological Abstracts 1926 • Abstracts of Bacteriology 1917 -26 • Botanical Abstracts 1918 -26 – Applied Science & Technology Abstracts 1932 – Excerpta Medica 1947

Biology A&I Services, cont. Note niche titles appearing in late ‘ 60 s – – – Science Citation Index (multidisciplinary) Genetics Abstracts* Nucleic Acid Abstracts * Amino Acid, Peptide, & Protein Abstracts BIOETHICSLINE Biology Digest * Biotechnology Research Abstracts * Derwent Biotechnology Abstracts Current Biotechnology Current Advances in Biochemistry Current Advances in Genetics and Molecular Biology 1961 1968 1970 1972 1973 1974 1982 1983 1984

Oncogenes and Growth Factors Abstracts * Plant Genetic Resources Abstracts Current Advances in Protein Biochemistry Applied Science and Technology Abstracts Bioengineering Abstracts Medical and Pharmaceutical Biotechnology Abstracts – Scopus (multidiscplinary) – – – 1989 1992 1993 2004 Trend for increased specialization of topical coverage of bibliographic databases * CSA Cambridge Scientific Abstracts

It Starts with DNA — The Molecule of Life

James Watson & Francis Crick 1962 • • DNA not a protein Erwin Chargaff – Equal number of A—T bases – Equal number of C—G bases • Linus Pauling – Helical shape of protein • X-Ray crystallography – Franklin’s Photo 51 • • Form of A, C, G, T bases Avery, Mac. Leod, & Mc. Carty – DNA linked to heredity • DNA “transforming factor” – Not cited • “oversight” Watson • Nobel with Maurice Wilkins – Rosalind Franklin died several years earlier

Physics Today, Vol. 56, no. 3, March 2003

Rosalind Franklin “The Dark Lady of DNA” – Determined chemical structure of DNA by molecular structure and X-ray crystallography • Photo of the DNA molecule taken by Rosalin Franklin • Photo shown to Watson by Maurice Wilkins, co-worker of Franklin and who shared Nobel Award with Watson & Crick • Photo 51 – She didn’t know her photo was shown to them See: • http: //www. pbs. org/wgbh/nova/photo 51/ • http: //eds. a. ebscohost. com/ehost/resultsadvanced? sid=e 5510096 -9 a 22 -41 b 2 b 50 c-e 9 f 6 e 395619 b%40 sessionmgr 4004&vid=2&hid=4111&bquery =(rosalind+franklin)+ AND+(SO+(physics+today))&bdata=Jm. Ri. PWE 5 a. CZ 0 e. XBl. PTEmc 2 l 0 ZT 1 la. G 9 zd. C 1 sa. XZl. Jn. Njb 3 Bl. PXNpd. GU%3 d

www. pbs. org/wgbh/nova/body/DNA-photograph. html

Its Multidisciplinary and New Search Language Emerges: Sequences http: //www. sciencecartoonsplus. com/gallery/biology/galbio 2 b. php#

A Brief DNA History: Friedrich Mieschler • “Friedrich Miesclher: The Man Who Discovered DNA” – by George Wolf in Chemical Heritage 21(2): 10 -11, 37 -41, 2003 – 1869 (not published until 1871) – Nuclein • Proteins 1838 – Gerardus Johannes Mulder – Jöns Jakob Berzelius – Leukocyte nuclei from (pus) • Looking for chemical composition • Almost entirely “nuclein” – Phosphate, nitrogen, no sulfur – Sperm of Salmo salar (Atlantic Salmon)

Albrecht Kossel Nobel Prize ~ 1910 Physiology & Medicine • Physiological chemist and medical doctor • Studied proteins and nucleins • Discovered a protein-like composition of nucleins • Also a non-protein component: nucleic acids – – – Adenine Cytosine Guanine Thymine Uracil • 1 st Nobel Prize (nucleic acids)

What They Started 2013 80000 70000 DNA & RNA Articles in Chemical Abstracts, 1893 -2011 Draft Human Genome 50000 Human Genome Project 40000 30000 1953 Nature DNA Papers 20000 Complete Human Genome 10000 0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70 73 76 79 82 85 88 91 94 97 100 103 106 109 112 115 118 No. Citations per Year 60000 Years from 1893 to 2011

Human Genome Completed 300 Citedness of Watson's & Crick's 1953 Papers in Nature (March and May) 250 Number of Times Cited + 200 Human Genome Started 1962 Nobel 150 Nature Papers 100 March Obliteration (Garfield, 1985) --PCR-- May Total 50 + + 0 1950 1960 1970 1980 Year 1990 2000 2010

“Making Sense of Next Big Things in Science” • Zabel, Diane, and Stankus, Tony • Reference & User Services Quarterly – Winter 2002, Vol. 42 Issue 2, p 110. 9 p. • Offers a model for collection development in emerging new areas of science and technology that offer huge economic market potential, a. k. a. , the Next Big Thing (NTB): in this case, the area of proteomics, or protein science. Aims to assist librarians in developing a strategy for collection building without having the advantage of the explicit advice of exhaustive studies with heavy-duty bibliometrics that have yet to materialize. Focuses on how to make enough sense of what scientists involved in proteomics are saying to one another in journals so that a librarian can begin to assemble a working collection, to be later followed by confirmation, modification or extension in light of what truly expert librarians have to say in neighboring fields. Explains how to correctly get the first few things bought for proteomics until sufficient experience with the newly recruited faculty allows for locally guided collection growth.

“Proteomics” • Marc Wilkins coined the term proteome in 1994 in a symposium in Siena in Italy. • It appeared in print in 1995 with the publication in Wilkins's Ph. D thesis. • Wilkins used the term to describe the entire complement of proteins expressed by a genome, cell, tissue, or organism. • First conference paper 1994 • First Use 1994 • First Dissertation 1994 • First article 1994 • First Book 1995 • First Review 1996 (153 Refs) • First Journal Title 2001 (Proteomics)

What Bibliometrics Tells Us "Proteomics" Journals 1995 --2014 7000 Web of Science Core 6000 Citations 5000 4000 Sci. Finder: CA 3000 2000 1000 0 1995 2000 2005 Year 2010 2015

New Kid on the Block: The “Microbiome” • Joshua Lederberg 2001 • “Totality of microorganisms and their collective genetic material present in or on the human body or in another environment. ” • The wide diversity of species that make up the microbiome is hard to fathom. http: //dictionary. reference. com/browse/microbiome http: //naturalmentor. com/how-your-gut-flora-prevents-you-from-getting-fat-and-sick/

Adding "Microbiome" 7000 6000 Citations 5000 4000 3000 2000 “Microbiome” Wo. S Core 1000 0 1995 2000 2005 Year 2010 2015

Human Genome Project ~ 1990 http: //www. genome. gov/10001772

http: //www. genome. gov/10001772

Managing the Data & Information www. ncbi. nlm. nih. gov Major Transition: Clinical & Therapeutic Outcomes, Translational & • Systems Biology • Established in 1988 • public databases, • conducts research in computational biology • develops software tools for analyzing genome data • disseminates biomedical information National Center for Biotechnology Information (NCBI)

Simple NCBI Directory GETTING STARTED • NCBI Education • NCBI Help Manual • NCBI Handbook • Training & Tutorials • Submit Data RESOURCES • Chemicals & Bioassays • Data & Software • DNA & RNA • Domains & Structures • Genes & Expression • Genetics & Medicine • Genomes & Maps • Homology • Literature • Proteins • Sequence Analysis • Taxonomy • Variation POPULAR Pub. Med Bookshelf Pub. Med Central Pub. Med Health BLAST Nucleotide Genome SNP Gene Protein Pub. Chem NCBI INFORMATION About NCBI Research at NCBI News NCBI FTP Site NCBI on Facebook NCBI on Twitter NCBI on You. Tube NLM NIH DHHS USA. gov FEATURED Genetic Testing Registry Pub. Med Health Gen. Bank Reference Sequences Gene Expression Omnibus Map Viewer Human Genome Mouse Genome Influenza Virus Primer-BLAST Sequence Read Archive National Center for Biotechnology Information (NCBI) U. S. National Library of Medicine 8600 Rockville Pike Bethesda MD, 20894 USA

Historic Growth of Genomic Data

NCBI: Ref. Seq Growth, 2004 -2014+ http: //www. ncbi. nlm. nih. gov/refseq/statistics/

Final Four

Animations of Biological Processes • Howard Hughes Medical Institute – www. hhmi. org/biointeractive/animations/index. html – Scroll ¾-down to Biological Clock Animations • • The Drosophila Molecular Clock Model The Human Suprachiasmatic Nucleus The Mammalian Molecular Clock Model Measuring Circadian Activity in Drosophila – View other animations for some interesting perspectives on chemistry driving molecular and structural biology

Chemical Controls of Biological Function • Per 1 & Per 2: “Biological Clocks” Circadian Rhythm • CRY Genes (Cryptochrome): light-independent inhibitors of circadian rhythm in mammals • BMAL & CLOCK: Genes encoding proteins regulating circadian rhythms • Dimer: Chemical structure of two similar monomers joined by weak or strong bonds • Animation – www. hhmi. org/biointeractive/media/mammalian_clock-lg. mov • Biochemical Analysis of the Canonical Model for the Mammalian Circadian Clock – www. ncbi. nlm. nih. gov/pmc/articles/PMC 3138243/

Staying Current • The Scientist – www. the-scientist. com/ • Chemical & Engineering News • Nucleic Acid Research – 1 st January: Database Reviews • Reviews and updates of database developments • 40 -50 articles per issue (1996 to present) – pubs. acs. org/cen/index. html • Science (AAAS) – www. sciencemag. org/content/v ol 291/issue 5507/ index. shtml • Nature – 1 st July: Web/Internet Reviews – www. nature. com/genomics/ • Reviews Web servers and services • 40 -50 articles per issue (2003 to present) • Bio-IT World – www. bio-itworld. com/index. html – nar. oupjournals. org/contents-by-date. 0. shtml

Structural & Molecular Biology & Genetics • Dynamic and mechanical processes of DNA replication and transcription – motor proteins translocate along, and rotate around DNA • • • carry out polymerization reactions, separate DNA strands, resolve topological issues, repair DNA damage, and modify DNA-binding proteins

DNA’s Structure Begins with Physics

80000 60000 50000 40000 30000 20000 No. Citations per Year 70000 DNA & RNA Articles in Chemical Abstracts, 1893 -2011 Original Papers 1953 Human Genome Nobel Project 1990 Prize 1962 PCR 10000 Complete Human Genome 2003 1 6 11 16 21 26 31 36 41 46 51 56 61 66 71 76 81 86 91 96 101 106 111 116 0 Years from 1893 to 2011

DNA & RNA Articles in Chemical Abstracts, 1893 -2011 80000 60000 50000 40000 30000 No. Citations per Year 70000 Nobel Prize 1962 Human Genome Project 1990 Original Papers 1953 PCR Complete Human Genome 2003 20000 1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73 77 81 85 89 93 97 101 105 109 113 117 0 Years from 1893 to 2011