ACTIP Bulletin 18

January 2000

In this issue:

Best scientific advances in 1999

Prediction: technologies to grow in 2000

ACTIP secure area

Computational technology and biotechnology

On the web

New Quality of Life Work Programme

News items (from BIA)

Best Scientific Advances in 1999

Top science - human stem cells

In their eleventh recognition of the top scientific developments of the year, the editors of Science have put the progress scientists have made towards understanding the potential of human stem cells at the top of the list. In one year, human stem cells have gone from uncharted territory to showing promise for treating numerous human diseases. In the "Top Ten" list, which appears in the 17 December issue, Science salutes this research and nine more of the year's hottest scientific developments for their profound implications for society and the advancement of science.

Among the other 9 topics shortlisted were two other biological ones: First Runner Up was Genomics, and also high scored the Ribosome Structure: 1999 witnessed the creation of the first maps of the ribosome's molecular structure.

Hot research!

As in previous years, the Editors of Science
have chosen six hot research areas to watch in the millennial year. This year
their choices are: enzymes in Alzheimer's disease, river restoration projects,
x-ray astronomy, epigenetics, nanocomputers, and polio eradication.

Top blunders and controversies

Science's Top Ten section also includes some additional awards. Blunder of the
Year goes to NASA's inadvertent use of English instead of metric units in
calculations that ultimately caused the demise of the Mars Climate Orbiter. The
Kansas Board of Education vote to drop evolution form statewide science
teaching standards has been dubbed the Breakdown of the Year, while the
Controversy of the Year was the debate over genetically modified foods.

Source: http://www.bioresearchonline.com/content/news/article.asp?DocID={32580694 -B3EC-11D3-9A7B-00A0C9C83AFB}

Prediction: technologies to grow in 2000

The following technologies and areas show some important signs of growth for the future:
* computer simulation-based biology. Low-cost but requires extensive real-world validation;
* Bioinformatics. Cheap to implement, but many players;
* Tissue engineering. Vast market, but difficult and expensive;
* gene switching. Multiple applications, but targeting and validation difficulties;
* Molecular cardiovascular disease drug discovery. Huge market but very long term.

The full article is available from the ACTIP Secretariat (reference Biotechnology 2000). Source: Nature Biotechnology, Vol 17, Dec 1999, pp 1239.

ACTIP Secure Area

The ACTIP website now features a secure area at:

www.ACTIP.org/manuals/secure.html

The page can only be accessed using a special username and password. ACTIP members and observers may request the username and password from the ACTIP secretariat.

The secure area features a number of interesting documents, and can be used by ACTIP members to post messages and documents of interest to other members.

The most recent addition are the minutes of the Brussels meeting. They are also in the mail to you.

Furthermore, the following regulatory documents are available in PDF format from the secure area:

EC Document 'A guideline on dossier requirements for Type 1 variations'

EC Document: Preliminary report - 'the evaluation of tests for the diagnosis of transmissable spongiform encephalopathy in
bovines'

FDA draft Guidance for industry 'supplemental guidance on testing for replication competent retrovirus in gene therapy and follow up of patients'

FDA Guidance for industry 'application of current statutory authorithy to nucleic acid testing of pooled plasma'

FDA Revised Guidance for industry on 'revised precautionary methods to reduce the possible risk of transmission of CJD and nvCJD by blood and blood products'

Please let us know whether you experience any problems in downloading these documents. The documents are also available from the ACTIP Secretariat upon request.

Computational technology and biotechnology

Extraordinary successes of the genome projects push the need for the development of more sophisticated and powerful computational techniques. Moving from sequence to structure to function, the computational requirements for both software and hardware will grow significantly.
Future developments will occur in genome modeling and annotation, comparative protein modeling and folding assignment, in silico drug design, mechanistic enzymology and modeling of cellular processes.

Source: Zhuan Chen of Key Media Systems at mikezchen@hotmail.com

Useful webaddresses about this topic are:

Databases

List of genome sequencing projects:
http://www-fp.mcs.anl.gov/~gaasterland/genomes.html

Bioinformatics WWW Sites:
http://biochem.kaist.ac.kr/bioinformatics.html

National Biotechnology Information Facility:
http://www.nbif.org/data/data.html

Human Genome Project Information:
http://www.ornl.gov/TechResources/Human_Genome/

EMBL WWW Services:
http://www.EMBL-heidelberg.de/Services/index.html

GenBank Database Query Form:
http://www.ncbi.nlm.nih.gov/genbank/query_form.html

Brookhaven Protein Data Bank WWW Server:
http://www.pdb.bnl.gov/

SWISS-PROT Protein Sequence Database:
http://expasy.hcuge.ch/sprot/sprot-top.html

European Bioinformatics Institute (EBI):
http://www.ebi.ac.uk/index.html

Stanford Genomic Resources (Yeast and Arabidopsis):
http://genome-www.stanford.edu/

Sequence Similarity Searches

Sequence similarity search at EBI:
http://www2.ebi.ac.uk/

NCBI: BLAST notebook:
http://www.ncbi.nlm.nih.gov/BLAST/

Alignment

Pairwise protein alignment (SIM):
http://expasy.cbr.nrc.ca/tools/sim-prot.html

ClustalW (multiple sequence alignment at BCM):
http://dot.imgen.bcm.tmc.edu:9331/multi-align/Options/clustalw.html

Prediction from Sequence

NIH Molecular Modeling Homepage (modeling homepage with links):
http://cmm.info.nih.gov/modeling/

PREDATOR (protein secondary structure prediction from single sequence):
http://www.embl-eidelberg.de/argos/predator/predator_info.html
NetStart 1.0 Prediction Server (neural network predictions of translation
start in vertebrate and Arabidopsis thaliana DNA):
http://www.cbs.dtu.dk/services/NetStart/

DNA repair predication
http://cbcg.lbl.gov/ssi-csb/Program.html

Other Resources

The International Society for Computational Biology:
http://www.iscb.org/

Center for Bioinformatics & Computational Genomics (CBCG)
http://cbcg.lbl.gov/

VSNS BioComputing Division:
http://www.techfak.uni-bielefeld.de/bcd/welcome.html

Internet Journal of Science - Biological Chemistry:
http://www.netsci-journal.com/

Bioinformatics Journal:
http://www3.oup.co.uk/bioinformatics/contents/

The Seventh International Conference on Intelligent Systems for Molecular
Biology:
http://ismb99.gmd.de/

Third Annual International Conference on Computational Molecular Biology
(RECOMB'99):
http://www.loria.fr/~kucherov/RECOMB99/

Pacific Symposium on Biocomputing '99:
http://www.cgl.ucsf.edu/psb/psb99/

Source: AgBiotech Bulletin, Dec 1999

On the web

Information service on EU Affairs

Euractive is a new, free information service on EU Affairs. It offers:
Polis- daily news and links on EU Affairs
Focus - process overviews, positions of EU actors and summaries
Guide - largest directory of EU actors, online, more than 10,000 contacts

I tried it and it is a very useful site.

www.euractive.com

Industry news

Visit the Bioresearch Online News and Analysis page for the latest industry
headlines and feature articles.

www.bioresearchonline.com

http://www.bioresearchonline.com/read/nl19991209/40491

New website ECACC

ECACC (European Collection of Cell Cultures) has joined forces with Sigma-Aldrich, a manufacturer and supplier of cell culture media and research reagents. It has redesigned its website, featuring more user friendliness, easily accessible catalogues, forms and information. Please note that ECACC is also organizing cell culture training courses. Visit:

www.camr.org.uk/ecacc.htm

EFPIA website

It was a long wait, but the website of EFPIA is finally up and running. The site features news, conferences, position papers, publications etc. Visit:

www.efpia.org

European Pharmacopoeia

The European Pharmacopoeia regularly organizes discussion days attended by professionals in the area of quality of medicines. It publishes the proceedings on its websites. For example, there are proceedings on a gene therapy session. Please check regularly:

http://www.pheur.org

Important EC websites

Below just to remind you, some important websites of the European Commission's Research Directorate:

Info package to submit a proposal:
www.cordis.lu/life/home.html

Quality of Life Bulletin:
www.cordis.lu/life/src/newslet.htm

Funded projects from previous programmes:
www.cordis.lu/scr/i_009_en.htm

Biotech & Finance Forum:
http://europa.eu.int/comm/dg12/biotech/finance.html

Marie Curie Industry Host Fellowship:
www.cordis.lu/improving/src/hp_mcf.htm

Innovation and SME programme:
www.cordis.lu/innovation-smes/home.html

New Quality of Life Work Programme

On December 15, 1999, the European Commission published in the Official Journal a new Call for Proposals for collaborative RTD actions for the Quality of Life and Management of Living Resources programme. The Call Identifier is 1999/C 361/07; a corrigendum has been published in the Official Journal OJ C 361/07. All documents, such as the Work Programme and the Guides for Proposers 1 and 2 are available from the CORDIS server. Please use the ACTIP website to access the CORDIS server (either use the interesting links page, or, if you are an ACTIP member or observer, use the secure area, which feautures direct links to the CORDIS server).

Below I will summarize some of the major objectives of Key Action 2 (Control of Infectious Diseases) and Key Action 3 (Cell Factory).

Key action 2: Control of Infectious Diseases

Deadline: October 11, 2000 for 2.1, 2.2 and 2.3.

Main objectives:
(1) to improve the prevention and treatment of infectious diseases of major public health importance through the development of new and improved preventive and/or therapeutic vaccines and vaccination strategies;
(2) to identify and exploit new targets for anti-infective interventions;
(3) to develop new diagnostic tests;
(4) to develop tools for epidemiological monitoring and forecasting;
(5) to develop the research base for rational public health practices related to infectious diseases.

A prinicple deliverable of this key action will be integrated Community-wide approaches for the development of control tools against major human and animal infectious diseases, mobilising relevant stakeholders towards that end.

Priorities for the 2000 calls are:

2.1. Development of improved or novel mono-component, multi-component and combined vaccines
2.1.1. New vaccination strategies;
2.1.2. Discovery phase and pre-clinical; development of preventive and therapeutic vaccines;
2.1.3. Clinical evaluation of vaccines.

2.2. Strategies to identify and control infectious diseases
2.2.1. Treatment of, and protection against, human and animal infectious diseases;
2.2.2. Antimicrobial drug resistance and changes in virulence;
2.2.3. Diagnostic tests for humans and animals.

2.3. Aspects of public health and care delivery systems
2.3.1. Risk assessment, transmission and surveillance;
2.3.2. Methodologies for medicinal product safety surveillance in the market place;
2.3.3. Organisational and economic aspects of human and animal health.

Key action 3: The Cell Factory

Main objectives:

The integration of innovative research and technologies with their exploitation by industry and/or other socio-economic entities in the fields of health, environment, agro-industry, agri-food and high value added chemicals. Particular attention will be given to the problem solving approach of strengthening European industrial competitiveness by improving the potential for creation of small research-based biotechnology firms and entrepreneurial initiatives.
This key action will mobilise the necessary operators to address the following objectives in a co-ordinated and convergent way, linking the ability to discover to the ability to exploit:

(1) innovative technologies mobilising mission-oriented research;
(2) exploitation of RTD results.

Priorities for the 2000 calls are:

Projects must combine excellent science and convincing exploitation strategies. Provided the projects do satisfy this prerequisite, they may address a wide spectrum of targets. Therefore, the following only give 'aspects for consideration', which are non-exhaustive examples.

3.1. Improving the diagnostic and therapeutic arsenal for health care

3.1.1. Development of new diagnostics;
3.1.2. Therapeutic substances;
3.1.3. Therapeutic strategies;
3.1.4. Novel in vitro testing as alternatives to animal testing.

Deadlines:
March 15, 2000 for 3.1.2, 3.1.4
October 11, 2000 for 3.1.1., 3.1.3.

3.2. Improving environmental sustainability

3.2.1. New bioprocesses for industrial efficiency, to avoid pollution, make use of bioaccumulable wastes and by-products, and treat waste water;
3.2.2. Bioassays and biosensors;
3.2.2. Biodegradation of recalcitrant chemicals nd bioremediation;
3.2.4. Biodiversity and ecological dynamics of natural and introduced populations;
3.2.5. Methods and strategies for safe use of new biomolecules and bioprocesses, for identifying recombinant organisms and their residues in the environment, and assessing their impact on human and animal health, to support Community policies.

Deadlines:
March 15, 2000 for 3.2.1., 3.2.3.
October 11, 2000 for 3.2.2, 3.2.4., 3.2.5.

3.3. New biological and biotechnological products and processes for agro-industry, agri-food and high-value added chemicals

3.3.1. Exploiting the cellular and molecular characteristics of organisms;
3.3.2. High value-added products and processes involving/derived from micro-organisms, plants and animals;
3.3.3. Functional biomolecules and biocatalysts;
3.3.4. Identification and sustainable use of metabolic and genetic diversity as a source of new valuable products.

Deadlines:
March 15, 2000 for 3.3.2, 3.3.3.
October 11, 2000 for 3.3.4.

Key action 6: the Ageing population and disabilities

Objectives:
To raise the issue of 'the ageing population' as a priority subject for Community-wide cross-sectoral multidisciplinary research, combining and integrating efforts in the biological, biomedical, psychological, economic and social fields. Specific objectives and deliverables are:
(1) to promote healthy ageing;
(2) to improve the management of age-related illnesses and to cope better with disability;
(3) to improve the basis for the policy and planning of social welfare systems.

Priorities for the 2000 calls are:
6.1. Age-related illnesses and health problems;
6.2. Determinants of healthy ageing and of well-being in old age;
6.3. Demographic and social policy aspects of population ageing;
6.4. Coping with functional limitations in old age;
6.5. Health and social care services to older people.

Deadlines:
March 15, 2000 for all action lines

RTD activities of a generic nature

To contain oversubscription, only the following parts of the generic activities will be open for the year 2000 deadline (and not be open in the year 2001)

Deadlines:
October 11, 2000 for all action lines mentioned below

7. Chronic and degenerative diseases, cancer, diabetes, cardiovascular diseases and rare diseases
7.1. Elucidation of the common underlying pathogenic mechanisms involved in diseases initiation, progression and maintenance, concentraing on three main approaches:
* inter and intra cellular signalling;
* cell proliferation, differentiation, regulation, apoptosis etc;
* modelling of disease processes through cellular, tissue, animal and in silico models and their validation in humans;
* understanding the role of metabolic, genetic and environmental factors.

8. Research into genomes and diseases of genetic origin
8.1. Genome analysis, i.e. investigation and development of new pharmaco-therapeutic approaches based on genomic knowledge;
8.2. Functional genomics and proteomics: functional interpretation of the human genome and model genomes relevant to human health; comparative genome analysis, high-throughput methods, integration laboratory and computational approaches.

9. Neurosciences
9.1. Cell communication;
9.2. Brain theories, computational neuroscience and neuroinformatics.

12. Bioethics
13. Socio-economic aspects of life sciences and technologies

14. Support for research infrastructures
14.1. Biological collections;
14.2. Biological information resources;
14.3. Clinical research facilities (i.e. European facilities for batch production for clinical trials);
14.4. Pre-clinical research facilities (i.e. facilities for development of in vitro systems or cell culture, breeding of animals).

Deadlines:
March 15, 2000; October 11, 2000

Individual Training Fellowships: April 12, 2000; October 11, 2000

Marie Curie Host Fellowships: February 1, 2000

Technology Stimulation: January 12, 2000; September 13, 2000

SME support: April 26, 2000

Accompanying measures: February 10, 2000; October 11, 2000

Proposals must nowadays be sent to:
European Commission
Quality of Life Programme
Research Proposals Office (ORBAN 8)
Square Frère Orban 8, B-1000 Brussels

News items

(source: BIA Neswcast)

The BIA has recently produced a new Position Paper on Animal Testing. Members can access this from our website on http://www.bioindustry.org/index.html

Researchers from the Institute for Genomic Research, Rockville, Maryland have
deciphered the genetic code of a bacterium which can withstand radiation at 3,000 times the level fatal to humans. Source: http://www.tigr.org/

Pharmacogenomics market set to reach $795 million by 2005 says report by FT
Pharmaceuticals. Further information:
mailto:info.pharma@ft.com
mailto:edwin.bailey@ft.com
FT news website http://www.ft.com (registration required)

Scientists working on the Human Genome Project have announced the sequencing of
Chromosome 22. Researchers at the Sanger Centre in Cambridge have published the results. It is thought that sequencing of all the other human chromosomes should be complete in 2 years' time.
Website: http://www.sanger.ac.uk

Americans for Medical Progress reports that US animal rights groups continue to
increase their income. It is estimated that the total budget of all animal rights groups in the US is above $300 million. Further information:
http://www.amprogress.org/ab amp.htm

Cases of tuberculosis have risen by more than one fifth in a decade in England
and Wales according to the Public Health
Laboratory Service.
http://www.phls.co.uk

The UK Biotech sector market capitalization is £6.633 bn

Short News

Certificate of Suitability to include TSE

Under European Directives 75/318/EEC amended and 81/852/EEC amended, a supplier of raw materials must provide clients in the pharmaceutical industry with proof that the purity of its product is suitably controlled by monographs of the European Pharmacopeia. This is the role of the Certificate of Suitability. Since 1994, more than 400 certificates have been granted by the European Directorate for the Quality of Medicines. On November 11-12, 1999, 242 experts participated in a meeting on the procedure for this Certificate of Suitability. They reviewed 5 years of practice, and recommend to extend the scope of this new procedure to products with a risk of TSE, to strengthen communication between partners and to improve transparancy of certificates.

Source: edQM, Council of Europe. Tel + 33 3 88 41 28 15. www.coe.fr

European Pharmacopeia on CD-ROM

Other news from the Council of Europe: The CD-ROM 2000 version of the European Pharmacopeia is available! It has been supplemented with 200 new or revised standards, entering into force on January 1, 2000. CD-ROM 2000 includes all the texts of the 3rd edition of the European Pharmacopeia and supersedes all the previous editions. It comprises nearly 1450 monographs, 276 general methods of analysis, the full list of 1300 reagents, 950 safety data sheets for chemicals or biologicals, and the latest catalogue of 1150 chemical reference substances or biological reference preparations. The CD-ROM 2000 is available in English, French and a bilateral version.

Contact: Mrs. Caroline le Tarnec, tel + 33 388 41 28 15; fax: + 33 388 41 27 71; email: info@pheur.org; web: www.pheur.org

Endocrine disruptors

CEFIC has established the Long-range Research Initiative (LRI). One of the projects running under that umbrella is the Endocrine Modulator Study Group (EMSG). The EU Commission's Environment Directorate has assured industry that the 'list of candidate substances for assessment in relation to endocrine disruption (ED)' that it intends to establish will not be used as a 'blacklist' to ban chemicals. Instead, the list would guide additional research and prioritize substances for testing.

At the end of September, the Environment Directorate invited 17 experts to start prioritising 116 substances on their effects on wildlife and mammals including humans. A final report on the establishment of a priority list is foreseen for mid-2000.

On the same topic:

* in April 1999, Sweden approved a new chemicals policy to ensure that all new products sold in 2020 in Sweden are free from endocrine-disrupting substances. In the shorter term, Sweden expects to have guidelines in place by June 2000 to reduce exposure to hazardous substances.

* as of January 2000, industry in Norway will be required to substitute all ED's and other hazardous substances by the least harmful alternative available.
* the US study of the National Academy of Sciences on ED's is inconclusive and more research is needed
* the US EPA drops massive ED screening programme because of failure to develop an automated HTPS system.

Source: LRI News

LRI: External Science Advisory panel

The same LRI has recently established an external Science Advisory Panel, composed of 11 leading scientists from across Europe. Panel members are Profs. Adami, Calamari, Calow, Kuper, Ray, Taylor, Van Leeuwen, Vos, Winneke, Yamasaki and Zehnder. The panel aims to ensure impartiality and transparency of LRI research.

6 Mio EURO for Pharming

The biopharmaceutical company Pharming has received 6 MioEURO support from Finnish and Dutch governments for the further development of human lactoferrin I and human Collagen type I, produced in the milk of transgenic animals (rabbits).

Consultancy in TSE

SEDECON 2000 is a new consultancy offered by Dr David M Taylor PhD MBE with regard to TSE-related problems, particularly those involving inactivation of the causal agents of TSEs. Contact:
Tel: +44 (0) 131 441 3897
Fax: +44 (0) 131 441 3897
e-mail: david.taylor@sedecon2000.
freeserve.co.uk

Publications

New antibiotics

The December issue of Nature Biotechnology (vol 17, Dec 1999, pp 1165-1169) contains a feature article on 'The new antibiotics - can novel antibacterial treatments combat the rising tide of drug-resistant infections?' A very interesting article, containing a review of all possible new antibacterial approaches and a listing of companies involved in the field. A copy is available from the ACTIP Secretariat.

Genome projects for medically important microbes

The same feature article mentioned above contains a gem of a table on genome sequencing projects for medically important microbes (Nature Biotechnology, Vol 17, Dec 1999, Table 2, pp 1168). It gives the micro-organisms, the genome size, the principal investigators, the disease caused by these micro-organisms and the status of the genome project. It lists 19 genome projects, and most are finished or near completion. A copy is available from the ACTIP Secretariat.

Future issues in biotechnology

The EFB and EMBO organized on April 7-9, 1999, a workshop on 'future issues in biotechnology'. A summary report of that workshop is now available from the ACTIP Secretariat, or from Dr. David Bennet, mail: efb.cbc@stm.tudelft.nl

Safety of GM Lactic Acid Bacteria

If you are interested in genetically modified (GM) lactic acid bacteria, you might be interested in a recent report of a workshop held in Geneva on 'The Application of Lactic Acid Bacteria in Food Products in Europe'. The report is available from the ACTIP Secretariat.

Regulatory Documents:

Available from the ACTIP secretariat on request
:
Draft on 1% threshold labelling of genetically modified corn and soya.

A defined risk approach to the regulatory assessment of the use of neoplastic cells as substrates for viral vaccine manufacture.

A guideline on Dossier Requirements for Type 1 variations.

EMEA concept paper on the development of a CPMP Points to Consider on cell-derived influenza vaccines.

EMEA Concept paper on a CPMP Points to Consider on Live Attenuated Influenza vaccines.

EC publications

The Commission has reported on its RTD activities in 1999. For example, it started in 1998 6,200 new projects under FP4 with over 28,000 participants. The report is available from DG Research, SDME 2/85, fax + 32 2 295 82 20, or at http://europa.eu.int/comm/dg12/report99.html.

The Commissions DG Information Society has created the Linking Innovation, Finance and Technology (LIFT)-programme in order to help research companies get funding for commercial projects. For more information: Fiona Mulhem, fax + 352 42 80 03; email: info@lift.lu

DG Research published the proceedings of a special session, called 'Researchers meet Entrepreneurs', which was held during ECB9 in July 1999. The proceedings also contain information on the IPR Helpdesk and the LIFT Helpdesk. A copy of these proceedings can be requested from the ACTIP Secretariat.