Microbiology in the 21st Century International Symposium on Designing the Microbial Research Commons

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Microbiology in the 21st Century


Our charge

  • 1. What are the research and applications opportunities from improved integration of microbial information within the global community?

  • 2. What are the challenges and barriers?



My charge

  • To represent microbiology and set the stage for our discussion.

  • I was asked to do an overview of “biomedicine and the environment.”



  • The charge was so broad and so challenging that I have decided to focus on the clinical to the exclusion of the environmental.

  • Further, it is impossible to talk about microbiology in the 21st century without talking about microbiology in the 20th century.



Outline

  • Definitions

  • Primer in microbiology

  • Professional societies, journals and culture collections

  • Microbiology, genetics and genomics

  • 21st century



1. Definitions



Common  

  • a. Belonging equally to or shared equally by two or more; joint: common interests.

  • b. Of or relating to the community as a whole; public: for the common good.

  • 2. Widespread; prevalent.

  • 3. a. Occurring frequently or habitually; usual.

  • b. Most widely known; ordinary: the common housefly.

  • 4. Having no special designation, status, or rank: a common sailor.

  • 5. a. Not distinguished by superior or noteworthy characteristics; average: the common spectator.

  • b. Of no special quality; standard: common procedure.

  • c. Of mediocre or inferior quality; second-rate: common cloth.

  • 6. Unrefined or coarse in manner; vulgar: behavior that branded him as common

  • http://www.thefreedictionary.com/Common



Commons

  • 1. commons The common people; commonalty.

  • 2. commons (used with a sing. or pl. verb) a. The social class composed of commoners.

  • b. The parliamentary representatives of this class.

  • 3. The House of Commons. Often used in the plural.

  • 4. A tract of land, usually in a centrally located spot, belonging to or used by a community as a whole: a band concert on the village common.

  • 5. The legal right of a person to use the lands or waters of another, as for fishing.

  • 6. commons (used with a sing. verb) A building or hall for dining, typically at a university or college.

  • http://www.thefreedictionary.com/Commons



"The Tragedy of the Commons," Garrett Hardin, Science, 162(1968):1243-1248.

  • "The Tragedy of the Commons," Garrett Hardin, Science, 162(1968):1243-1248.





2. Primer in microbiology

  • Microbiology for dummies



Microbiology

  • Microbiology is the study of organisms that are too small to be seen by the naked eye.

  • A microscope is needed to see the individual cells of microbes.



What life forms?

  • The major groups of microbes are archeae, bacteria, viruses, protozoa, fungi and algae.

  • The cognate disciplines are bacteriology.

  • virology, protozoology, mycology and phycology.



Microbiology is experimental.

  • Because microbes are so small, early microbiologists figured out ways to grow them in the laboratory so we could see populations of them growing together in colonies.

  • Many of the early techniques were developed by 19th century bacteriologists.



Nature provides its own ways of seeing colonies



Prior to the microscope, microbes also were known indirectly, by what they did





Infectious disease= pathogen-caused disease

  • An infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular parasites, and the aberrant proteins known as prions.



Examples of bacterial diseases

  • Leprosy

  • Gonorrhea

  • Syphilis



Plague: the Black Death

  • In the early 1330s an outbreak of bubonic plague occurred in China. In October of 1347, several Italian merchant ships returned from a trip to the Black Sea. Within days the disease spread to the city and the surrounding countryside. By the following August, the plague had spread as far north as England, where people called it "The Black Death" because of the black spots it produced on the skin. …Each spring, the plague attacked again, killing new victims. After five years 25 million people were dead--one-third of Europe's people. http://www.themiddleages.net/plague.html



Examples of viral diseases

  • AIDS

  • Herpes

  • Measles

  • Small pox







Koch’s postulates

  • The microorganism must be found in abundance in all organisms suffering from the disease, but not in healthy organisms.

  • The microorganism must be isolated from a diseased organism and grown in pure culture.

  • The cultured microorganism should cause disease when introduced into a healthy organism.

  • The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.



3. Professional societies, journals and culture collections



Professional societies

  • The American Society for Microbiology (ASM) is the world's largest –and one of the oldest - life science membership organizations. Beginning with 59 scientists in 1899 as the Society for American Bacteriologists (SAB), ASM now has over 40,000 members, representing 24 disciplines of microbiological specialization plus a division for microbiology educators.

  • http://cbe.wisc.edu/cels/monograph/mono6x17.htm



Bergey's Manual of Determinative Bacteriology

  • The first edition of was initiated by action of the Society of American Bacteriologists (now called the American Society for Microbiology) by appointment of an Editorial Board consisting of David H. Bergey and others. This Board, under the auspices of the Society of American Bacteriologists who, then as now, published the Journal of Bacteriology as a service to science, brought the first edition of the Manual into print in 1923. The Board, with some changes in membership and Dr Bergey as Chairman, published a second edition of the Manual in 1925 and a third edition in 1930.



Society for General Microbiology (UK)

  • The Society publishes four journals : International Journal of Systematic and Evolutionary Microbiology

  • Journal of General Virology

  • Microbiology

  • Journal of Medical Microbiology

  • And one magazine: Microbiology Today.



INTERNATIONAL UNION OF MICROBIOLOGICAL SOCIETIES -IUMS

  • IUMS was founded in 1927 as the International Society of Microbiology, and became the International Association of Microbiological Societies affiliated to the International Union of Biological Sciences (IUBS) as a Division in 1967. It acquired independence in 1980 and became a one of the 29 scientific unions Member of International Council of Science (ICSU) in 1982.

  • IUMS is an umbrella for the many national microbiology societies.



IUMS

  • The first International Congress for Microbiology was held in Paris in 1930. At the time of the 10th International Con­gress of Microbiology held in Mexico in 1970 the Executive Committee decided to create three sections covering the fields of Bacteriology, Virology and Mycology.



World Federation of Culture Collections

  • The WFCC is a Multidisciplinary Commission of the International Union of Biological Sciences (IUBS) and a Federation within the International Union of Microbiological Societies (IUMS). The WFCC is concerned with the collection, authentication, maintenance and distribution of cultures of microorganisms and cultured cells. Its aim is to promote and support the establishment of culture collections and related services, to provide liaison and set up an information network between the collections and their users, to organize workshops and conferences, publications and newsletters and work to ensure the long term perpetuation of important collections.



WFCC World Data Center for Microorganisms (WDCM).

  • The WFCC (through the activities of Professor Skerman, University of Queensland, Australia, and his colleagues in the 1960's) pioneered the development of an international database on culture resources worldwide. The result is the This data resource is now maintained at National Institute of Genetics (NIG), Japan and has records of nearly 476 culture collections from 62 countries. The records contain data on the organization, management, services and scientific interests of the collections. Each of these records is linked to a second record containing the list of species held.

  • http://www.wfcc.info/aboutwfcc.html



World Federation of Culture Collections (http://www.wfcc.info)

  • The Education and Capacity Building Committee is in charge of the training of culture collection personnel in other collections

  • In the Patents and Intellectual Property Rights Committee, the emphasis is on the formulation of a universal material transfer agreement and an agreement for royalties.

  • The Transport, Quarantine and Safety Regulations Committee is concerned with continuing the inventory and the harmonization of the international rules, directives and laws that are applicable to the risk classes of organisms.

  • The Networking and Interoperability Committee elaborates links between the collections and to DNA databases, and evaluates the principles of knowledge management with regard to the linked databases.

  • The Standardization and Normalization Committee deals with the standardization and normalization for the completion of the "Guidelines for the Establishment and Operation of Collections of Cultures of Microorganisms" (2nd ed., 1999).

  • The Endangered Collections Committee investigates the condition of endangered collections,



  • A useful link:

  • http://wdcm.nig.ac.jp/hpcc.html

  • Home Pages of Culture Collections in the World



All of these efforts are under staffed and underfunded.



4. Microbiology, genetics and genomics



Microbiology has played a central role in the development of genetics and molecular biology



DNA is the genetic material

  • Avery, MacLeod and McCarty Studies on the chemical nature of the substance inducing transformation of pneumococcal types. (1944, in Experimental Medicine, vol. 79). --demonstrated that the “transforming principle” was DNA not protein.



Recombinant DNA

  • In 1972 American biochemist Paul Berg (1926–) developed a technique to splice DNA fragments from different organisms and created the first "recombinant" DNA, or DNA molecules formed by combining segments of DNA, usually from different types of organisms. In 1980 Berg was awarded the Nobel Prize in chemistry for this achievement, now referred to as "recombinant DNA technology."

  • http://www.libraryindex.com/pages/2219/History-Genetics-MILESTONES-IN-MODERN-GENETICS.html#ixzz0TKi3hURQ



Genetic engineering –con’t

  • In 1976 an artificial gene inserted into a bacterium functioned normally. The following year, DNA from a virus was fully decoded, and three researchers, working independently, developed methods to sequence DNA — in other words, to determine how the building blocks of DNA (the nucleotides A, C, G, and T) are ordered along the DNA strand. In 1978 bacteria were engineered to produce insulin, a pancreatic hormone that regulates carbohydrate metabolism by controlling blood glucose levels. Just four years later, the Eli Lilly pharmaceutical company marketed the first genetically engineered drug: a type of human insulin grown in genetically modified bacteria.

  • http://www.libraryindex.com/pages/2219/History-Genetics-MILESTONES-IN-MODERN-GENETICS.html



Diamond v. Chakrabarty

  • Genetic engineer Ananda Mohan Chakrabarty, working for General Electric, developed a bacterium (a strain of Pseudomonas) capable of breaking down crude oil, which he proposed to use in treating oil spills. He requested a patent for the bacterium in the United States but was turned down by a patent examiner, because the law dictated that living things were not patentable.

  • The Board of Patent Appeals and Interferences agreed with the original decision; however, the United States Court of Customs and Patent Appeals overturned the case in Chakrabarty's favor, writing that "the fact that micro-organisms are alive is without legal significance for purposes of the patent law." Sidney A. Diamond, Commissioner of Patents and Trademarks, appealed to the Supreme Court.



“Patenting life” 1980

  • In a 5–4 ruling, the court ruled in favor of Chakrabarty, and upheld the patent, holding that:

    • A live, human-made micro-organism is patentable subject matter under [Title 35 U.S.C.] 101. Respondent's micro-organism constitutes a "manufacture" or "composition of matter" within that statute.


Polymerase chain reaction -PCR

  • The 1985 invention of the polymerase chain reaction (PCR), which amplifies (or produces many copies of) DNA, enabled geneticists, medical researchers, and forensic specialists to analyze and manipulate DNA from the smallest samples.

  • In 2003, Ricki Lake and Bernard Possidente described American biochemist Kary Mullis's (1944–) development of PCR as the "genetic equivalent of a printing press" The work was done under while Mullis was employed at now defunct biotechnology company called Cetus. http://www.libraryindex.com/pages/2219/History-Genetics-MILESTONES-IN-MODERN-GENETICS.html#ixzz0TKjeydNO



Genome and genomics





Microbiology and genomics

  • Genomics was born out of tools developed within the microbiological sciences:

  • Bacterial and phage genetics

  • Gene splicing and genetic engineering

  • Direct DNA sequencing accomplished using microbial vectors



Early milestones in genomics (USA)

  • 1988 Office of Genome Research

  • National Institutes of Health

  • National Center for Genome

  • Research

  • 1990 Human Genome Project (HGP)

  • initiated



Genomes decoded

  • In 1995 investigators at the Institute for Genomic Research published the first complete genome sequence for any organism: the bacterium Haemophilus influenzae, with nearly two million genetic letters and 1,000 recognizable genes. The following year the yeast genome, composed of about 6,000 genes, was sequenced, and in 1997 the genome of the bacterium E. coli, which contains approximately 4,600 genes, was sequenced.

  • http://www.libraryindex.com/pages/2219/History-Genetics-MILESTONES-IN-MODERN-GENETICS.html#ixzz0TKkbMGTV





20th century milestones in bioinformatics

  • 1981 - The Smith-Waterman algorithm for sequence alignment is published. 1982 GenBank established (NIH - USA)

  • 1988 National Center for Biotechnology Information (NCBI) created

  • 1990 BLAST algorithm (Lipman and colleagues at NCBI)

  • 1993 Sanger Centre, Hinxton, UK

  • 1994 EMBL European Bioinformatics Institute, Hinxton, UK

  • 1997 PSI-BLAST



5. 21st century

  • Microbiology and more



Why we are here:

  • Materials

  • Literature

  • Data bases

  • Each area brings different economic, historical, institutional and legal baggage



Materials



Essential resources for the community

  • Stable, well curated resources of living stocks.

  • Microbes are used as a resource in a number of industries.



World Federation of Culture Collections

  • Type strains – references for taxonomy/systematics

  • Model strains

  • Patent deposits

  • Need quality management controls – best practices



Physical resources

  • Cultures themselves: fungi, protozoa, bacteria, viruses (plasmids)

  • Issues concern quality control, toxicity, security, and sustainability



Digital resources

  • Taxonomic data

  • Strain information

  • Genetic sequence data

  • Relevant literature

  • Data bases



Basic/applied research

  • Financial returns – intellectual property rights

  • MTA – material transfer agreement…”now treat every biological deposit as if it were of potentially commercial value.” (pg. 30)



1% OF WORLD’S MICROBIAL RESOURCES KNOWN

  • “Rather than distorting the open access values of the entire research semicommons to accommodate this limited set of material shave downstream commercial opportunities…pg. 47 draft for Microbial Commons.



Convention of Biological Diversity

  • Quite restrictive access measures in several developing countries, likely as a reaction to the excess of bio-prospecting and patenting from developed countries in the past.

  • (pg. 33 – draft Microbial Commons)



Literature



PRIORITY

  • “There is a universal understanding in science that the first discover must have either a right to first publication or at least an embargoes period of exclusivity during which that the discoverer cannot be pre-empted by second comers having access to the same research materials. These and related norms of science tend to preserve the reputational benefits that are known to be the primary motivator of the not-for-profit scientific activity” (pg 42 –draft Microbial Commons)



Scholarly publication

  • Scientists submit work to a recognized journal; work reviewed by editors and reviewers (unpaid). The system provides a gate keeping function that ensures quality and yields reputational benefits. Professional societies and commercial publishers produce the journals.



Commercialization of scholarly publishing: librarian perspective

  • Perhaps the greatest impediment to communications is that academic societies have turned to commercial publishers to produce their journals.

  • Average cost of a chemistry periodical in 2009 was $3690.

  • (Library Journal Periodicals Price Survey)



Library costs

  • Between 1986 and 2006, journal expenditures of North American research libraries increased by a staggering 321% as libraries expanded access to journals by licensing bundles of journals (e.g., Science Direct) from different publishers (e.g., Elsevier). At the same time, the average journal cost increased by 180% while the U.S. Consumer Price Index rose by 84%. In other words, journal costs have outstripped inflation by a factor of more than two. http://www.uic.edu/depts/lib/projects/scholcomm/costs.shtml



Cornell University

  • In its December 17, 2003 resolution, the Cornell University Faculty Senate delivered a scathing indictment of the commercial science publishing industry and especially of Elsevier, the giant which now owns such venerable publishers as Academic Press. (The resolution was updated on May 11, 2005. Faculty senates of Ivy League schools have not been known to be gathering places of revolutionary hotheads, so the strong language used in the Cornell resolution deserves special attention. The resolution does not mince words. It uses phrases like "crisis in the cost of journals," "literally unbearable," "unsustainable," "threatens to undermine core academic values," "Elsevier's prices are radically out of proportion with the importance of those journals..." http://theoryofcomputing.org/crisis.html



  • Publishers used to do the typesetting of papers; thanks to TeX, nowadays the authors do the typesetting. Publishers used to perform an essential service by distributing the scientific papers; thanks to the Web, this service is no longer needed. Why should the community subsidize, with enormous investment of volunteer work, commercial enterprises that take away the copyright, charge exorbitant fees, and restrict access to the online versions of their publications? (It only adds to the irony that virtually every mathematics and CS journal uses some version of TeX, created with great care and distributed free of charge by Don Knuth.)

  • http://theoryofcomputing.org/crisis.html



  • Publishers have sought to configure the online environment on the model of print media.



Free full text journal articles

  • Microbiology and Molecular Biology Reviews, Applied and Environmental Microbiology, Applied Microbiology, Bacteriological Reviews, BMC Immunology, BMC Infectious Diseases, BMC Microbiology, Clinical and Diagnostic Laboratory Immunology, Clinical and Molecular Allergy, Clinical Microbiology Reviews, Infection and Immunity, Journal of Bacteriology, Journal of Clinical Microbiology, Journal of Immune Based Therapies and Vaccines, Journal of Virology, Medical Immunology, Microbiology and Immunology, International Microbiology, Retrovirology, Virology Journal, Microbial Cell Factories, Antimicrobial Agents and Chemotherapy, and Malaria Journal.

  • http://www.neurotransmitter.net/fulltextmicrobiology.html



ASM Journals Public Access Policy

  • “ASM provides free access to full-text articles 6 months after the final version is published in an issue of one of the 9 primary research journals. For the review journals, Clinical Microbiology Reviews  and Microbiology and Molecular Biology Reviews, access to full-text articles is made freely available 1 year after an issue's publication. Tables of contents, abstracts, and search features are freely available to all users.”

  • http://journals.asm.org/misc/index_compliance.dtl



NIH Policy and ASM

  • Effective April 2008, the NIH initiated a policy requiring that all investigators funded by the NIH either submit or have submitted for them to the National Library of Medicine’s PubMed Central an electronic version of their final peer-reviewed manuscripts upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication. Authors of ASM journal articles are automatically in compliance with this policy and need take no action themselves.

  • http://journals.asm.org/misc/index_compliance.dtl



Databases



“-omes” and “-omics”

  • Transcriptome – all the RNA transcripts of an organism

  • Proteome – all the proteins of an organism

  • Metabolome – all the metabolites of an organism

  • (and many, many other variants)



  • Convergence of microbial and genomics research

  • In silico research – computational biology



Characteristics of “omics” research

  • Huge data sets

  • High throughput” (i.e. fast, automated) methods for collecting data

  • Computers and mathematics

  • These methods facilitate a new kind of biologist who does “in silico” research.



20th Century enabling technology for DNA synthesis

  • 1981 high throughput robotic detection (Hitachi and Wada) – later incorporated into ABI technology

  • 1986 – First commercial DNA sequencer ABI Prism 370 1000 bases / day

  • 1995 capillary electrophoresis ABI (Prism 310) 5000-15,000 bases / day

  • 1998 PE Biosystem – Prism 3700 multiple capillary 500,000-1 million bases/ day



“Sequencing by synthesis”

  • Roche (454) 450 bp

  • Illumina (Genome Analyzer) 50 – 100 bp

  • ABI (SOLID) 50-100 bp

  • 20 million bases /run? More?

  • Sequencing technologies evolve very fast. We mycologists need to collaborate with the best sequencing centers with the fastest and/or most appropriate technologies.



  • Data generation – huge

  • Data manipulation - huge

  • Massive storage capacity



The psychological impact of genomics as expressed in metaphors

  • Wealth

  • Explosion

  • Avalanche

  • Tidal wave/tsunami

  • Deluge

  • Flood



Fewer positive metaphors

  • Wealth

  • Data mining



  • The rate of change in new technological systems outpaces human capacity to adopt to the technological advances, much less to exploit those advances for maximum social and economic benefits.”

  • (pg 55 – draft Microbial Commons)



Our challenge



The Convention on Biological Diversity

  • What is the Convention?

  • “Signed by 150 government leaders at the 1992 Rio Earth Summit, the Convention on Biological Diversity is dedicated to promoting sustainable development. Conceived as a practical tool for translating the principles of Agenda 21 into reality, the Convention recognizes that biological diversity is about more than plants, animals and micro organisms and their ecosystems – it is about people and our need for food security, medicines, fresh air and water, shelter, and a clean and healthy environment in which to live.”

  • http://www.cbd.int/convention/



  • Article 15. Access to Genetic Resources

  • 1. Recognizing the sovereign rights of States over their natural resources, the authority to determine access to genetic resources rests with the national governments and is subject to national legislation.



WIPO Copyright Treaty adopted in Geneva on December 20, 1996)

  • WIPO Copyright Treaty adopted in Geneva on December 20, 1996)

  • Art. 2. (Scope) Copyright protection extends to expressions and not to ideas, procedures, methods of operation or mathematical concepts as such.

  • Art. 5 (Databases) Compilations of data or other material, in any form, which by reason of the selection or arrangement of their contents constitute intellectual creations, are protected as such. This protection does not extend to the data or the material itself and is without prejudice to any copyright subsisting in the data or material contained in the compilation.

  • http://www.wipo.int/treaties/en/ip/wct/trtdocs_wo033.html#preamble



A problem

  • WIPO was designed for writer and entertainers, not for scientists.



What is the WTO?

  • “The World Trade Organization (WTO) is the only global international organization dealing with the rules of trade between nations. At its heart are the WTO agreements, negotiated and signed by the bulk of the world’s trading nations and ratified in their parliaments. The goal is to help producers of goods and services, exporters, and importers conduct their business.” http://www.wto.org/english/thewto_e/whatis_e/whatis_e.htm



  • “In practice, these provisions – written by lawyers for lawyers – have nothing to do th science and could not be understood or used by scientists….

  • After a long discussion of EC Infosco pg 110 – draft for the Microbial Commons)



Hope

  • The genome sciences, less encumbered by past traditions, societies and journals and born during the Internet era have done the best job of creating scientific commons, including from microbiology.



GenBank Data Usage http://www.ncbi.nlm.nih.gov/Genbank/

  • “The GenBank database is designed to provide and encourage access within the scientific community to the most up to date and comprehensive DNA sequence information. Therefore, NCBI places no restrictions on the use or distribution of the GenBank data.”



European Bioinformatics Institute EBI

  • A vast multi-dimensional “information space” built up over many years by the genomic research community and coordinated body by EBI…operate under the rules of public science, …scrutiny by the global research community (pg 58 – draft of Microbial Commons)



Standards in Genomic Sciences, Vol 1, No 1 (2009)

  • The Genomic Standards Consortium (GSC) is an initiative working towards richer descriptions of our collection of genomes and metagenomes through the development of standards and tools for supporting compliance and exchange of contextual information. Established in September 2005, this international community includes representatives from the International Nucleotide Sequence Database Collaboration (INSDC), major genome sequencing centers, bioinformatics centers and a range of research institutions.

  • http://www.standardsingenomics.org/index.php/sigen/article/viewArticle/sigs25165/53



Standards in Genomic Sciences, Vol 1, No 1 (2009)

  • The rapid pace of genomic and metagenomic sequencing projects , which now include studies of microbiomes, will only increase as the use of ultra-high-throughput sequencing methods becomes more common place. Therefore, the role of standards becomes even more vital to scientific progress and data sharing. It is clear that we need new standards to capture additional contextual data as well as tools to support its use in downstream computational analyses. The GSC aims to hold workshops designed to allow the community to advance identified GSC projects and propose new ones. Face-to-face workshops also help to grow GSC membership and broaden linkages between the GSC and related projects within the wider scientific commons. http://www.standardsingenomics.org/index.php/sigen/article/viewArticle/sigs25165/53



The vision for the Genomic Rosetta Stone (GRS) project

  • The GSC is creating a mapping of identifiers describing complete genomes across a wide range of relevant databases so that information about genomes and the organism from which they derive can be more easily integrated. This mapping will include as many genomic databases as possible. The development of this "Genomic Rosetta Stone" (GRS) is core to the aim of auto-populating the Genome Catalogue with metadata harvested from other sources.

  • http://darwin.nerc-oxford.ac.uk/gc_wiki/index.php/Genomic_Rosetta_Stone



Infectious diseases

  • Continue to emerge

  • Continue to fund much of life science research



The microbial sciences have entered popular culture which helps with funding.



Nevertheless, we have our work cut out for us



The end of my lecture is the beginning of our real work.

  • Thank you!




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