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Australasian Biotechnology, Vol. 10 No. 1, 2000, pp. 18-21 INTERNATIONAL NEWS Code Number: au00008
US research suggests that mutations in mitochondrial DNA may provide a warning about the prevalence of cancer of the bladder, neck, head and lung. As reported in Science, the head of otolaryngology and oncology at John Hopkins University School of Medicine, Professor David Sidransky, said that mitochondrial mutations detected in bodily fluids were identical to mutations found in cancerous tumours of the bladder, head, neck and lungs. The finding potentially opens the way for simple non-invasive tests for early stages of cancer. HUMAN GENOME ANNOUNCEMENTShares in a number of listed US biotechnology stocks fell sharply in the wake of the joint statement by the US President and the UK Prime Minister calling for the raw data from the human genome project to be freely available. In the immediate aftermath of the announcement on March 15, the Nasdaq Biotechnology Index fell by 14.3%, with Celera Genomics Group falling by 21%. Celera, part of PE Corporation, is leading in the race to map the entire human DNA. It has forecast it will complete the sequencing this year. Celera is competing against the Human Genome Project, a non-profit partnership between the US National Institute of Health, the US Department of Energy and the British Wellcome Trust philanthropic organisation. The partnership is intending to publish a rough draft of the human genome map this year and has catalogued about one-third of the human DNA. The Human Genome Project releases its results daily on the Internet. Celera has not released any data to date but says it will do so when the project is finished. In their statement, President Clinton and Prime Minister Blair specified that 'gene-based inventions' could be patented, but argued that fundamental genetic data should be freely available for research. It is not believed that the two governments are planning any legislative enforcement to back up their call for public data to be accessible. NEW CHOLESTEROL TESTCholestech Corporation (NASDAQ:CTEC) announced in December the commercial availability and initial shipment of the Company's liver function test alanine aminotransferase (ALT) - also known as serum glutamic-pyruvic transaminase (SGPT). ALT quantitative measurements are used by physicians in the diagnosis and treatment of certain liver diseases (e.g. viral hepatitis and cirrhosis) and heart diseases. With the growing use of effective lipid-lowering therapies comes an increased need to monitor ALT. A side effect of these drugs can be a persistent increase in serum ALT levels, to more than 3 times the upper limit of normal, in about 1% of the patients receiving such therapy. The Company believes that, with the addition of the ALT test, the Cholestech LoDoX System will soon be able to provide a new level of diagnostic testing convenience for healthcare providers involved with monitoring lipid lowering and diabetes related drug therapies. GlycoDesign signs with SeikagakuInflammatory diseases will be the focus of a three-year research collaboration between GlycoDesign Inc. and Seikagaku Corp. (SKK) of Tokyo, Japan, a pioneer in the R&D of complex carbohydrates for medicines. Christian Frayssignes, Vice President of Business Development at GlycoDesign, told Canadian Biotech News that the collective expertise in glycobiology of the two companies will be employed to identify small molecule, orally active Core 2 transferase inhibitors for the treatment of inflammation. During the term of the research collaboration, SKK can select for development up to three compounds displaying anti-inflammatory activity. The research agreement also provides SKK with the option to an exclusive, worldwide, sub-licensable right, on a compound-by-compound basis, to license intellectual property covering compounds selected during the term of the collaboration. Core 2 transferase plays a key role in initiating the creation of carbohydrates that contain sialylLewis* (sLe*) structures. sLe* in turn is responsible for bringing leukocytes to the surface of damaged tissue, ultimately resulting in inflammation. A current approach in the development of anti-inflammatory compounds is to try to find ways to directly block the carbohydrate-based leukocyte recruitment. ClycoDesign's approach is different in that it is creating an oral inhibitor of Core 2 transferase that will prevent the synthesis of sLe* for extended periods and thereby arrest the progress of inflammation. Ginger May Help Fight CancerGinger may soon prove to be more than just a mere condiment in Thai cooking. Scientists have found that two kinds of ginger roots contain substances which can inhibit spontaneous mutations. Usually, such mutations lead to the development of cancer. However, the Japan International Research Center for Agricultural Sciences has identified eight anti-cancer substances in the two ginger roots native to Thailand called galanga and kra-chai. Using the Ames test, the researchers have been able to gauge the cancer-fighting abilities of the ginger's substances. In the Ames test - generally used to determine the carcinogenicity of chemicals - bacteria are exposed to a test sample to measure the extent to which mutations arise. BIOTECHNOLOGY DEVELOPMENTS IN JAPANThe presidents and chairmen of Japan's biotechnology firms have established the Japan Association of Bioindustries Executives (JABEX) as a coalition to promote the nation's biotechnology industry. The new organisation has submitted to the Japanese Government an opinion entitled "Recommendations to Improve International Competitiveness of the Nation's Biotechnology Industry". JABEX also invited the heads of five related ministries and the members of the alliance of Diet MPs for promoting life science to a round-table conference to brief the need for implementing the Helix Plan, a comprehensive nation-wide strategy to promote the commercialisation of biotechnology. The Plan has three major components including the Sun Helix Plan to realise a society with advanced healthcare, the Eco-Helix Plan to change the current industrial structure to an environmentally compatible one, and the Info-Helix Plan to realise a society that makes a maximum use of biological information. The JABEX representatives emphasised the need for urgently constructing the technological infrastructure including: (1) the acceleration of genome analysis; (2) the conservation of bioresources and securing their availability; (3) the utilisation of bioinformatics and the information networking of biotechnology research (full-length cDNA clones and SNPs) output. JABEX has also convened the first meeting of the Green-Bio Strategy Forum. Tadasu Tachi, a Counsellor of Kaneka Corporation, was elected Chairman. The forum, comprised of the presidents and chairmen of the 30 biotechnology-related firms from the chemical, pharmaceutical, food processing, construction and other industries, will promote "green" biotechnologies based on Japanese strength in enzyme and process technologies combined with genomics and metabolic engineering. BIA ChairmanThe Bioindustry Association (BIA) of the UK has elected Dr Paul Haycock as its Chairman for the year 2000. Dr Haycock is Chairman of bioscience companies Rademacher and Ribotargets, and Director of Apax Partners & Co, a leading UK venture investment company. Dr Haycock graduated in medicine from London University and completed postgraduate studies at the University of British Columbia. After five years' clinical practice in Canada, Dr Haycock moved into pharmaceutical and clinical research with Roussel Uclaf and later obtained a Diploma in Pharmaceutical Medicine and an MBA from the Cranfield School of Management. Virus ThreatKnowledge of wildlife diseases is crucial to predicting and possibly preventing threats to livestock and human health, a team of international scientists has warned. In a review published in Science, the authors describe how new diseases such as Australian bat lyssavirus, Lyme disease, and Nipah virus have moved on from wildlife hosts. "We live in close association with domestic and wild animals, sharing their habitat as well as their pathogens" says Peter Daszak of the University of Georgia, USA. "The point is that as we expand our population and encroach further into wild animal habitats, we cause the correct conditions for contact with these pathogens and the emergence of new diseases." CSIRO Animal Health's Dr Alex Hyatt says Australia has been affected by a number of these newly emerging viruses. "For example Hendra virus, which is carried by fruit bats and is lethal to horses and humans, shows that we need a greater understanding of the diseases of wildlife to be able to deal with threats to human and veterinary health, biodiversity and trade. Very little is known about wildlife diseases, because their link with ailments of humans and domestic animals has not been properly recognised in the past," he says. Pesticide reductionA recent Iowa State University study shows that farmers in the Mid West of the United States, who planted Bt (genetically modified, GM) corn (maize) from 1996 to 1998, succeeded in reducing their insecticide use each year. Bt maize is genetically engineered to produce a protein that is toxic to some insects, including the European corn borer. The insects die after feeding on GM maize leaves and stalks. Researchers confirmed that 26 per cent of the farmers who planted the GM maize in 1998 decreased their insecticide use. That is compared to the 19 per cent of GM maize farmers in 1997 who reduced their insecticide use, and 13 per cent of GM maize farmers who decreased their use of pesticides in 1996. About 1 in 2 of the GM maize farmers who were questioned said that they do not use insecticides. Marlin Rice, an Iowa State entomology professor who led the research team said: "These are farmers who are greatly cutting back their insecticide use or eliminating it altogether. The number of farmers reducing their insecticide use continues to rise dramatically each year, which I think the general consumer population would see as a favourable thing." Rice put the results in context by adding that of the 75 million acres that were planted with corn in the Mid West in 1998, 22 million acres were genetically modified maize. Taking the survey results - that 26 per cent of the farmers planting GM maize reduced their pesticide use - Rice said that research revealed that approximately 6 million more acres of land had less insecticide or no insecticide applied in 1998. Professor Rice believes that the survey results could help to establish an alternative view on GM crops and the maize hybrid, which has been cited as having potential detrimental effects on the caterpillars of the monarch butterfly. Marlin Rice concluded: "I believe it's important to put some balance into this argument. There are some environmental benefits being gained from this technology. It's not all negative about genetic engineering - this is on the positive side." Celera Compiles DNA SequenceUS corporation, Celera Genomics, a PE Corporation business, says it is on target to complete the sequencing phase of the human genome by summer 2000, incorporating data from GenBank. After sequencing, Celera then plans to begin shotgun sequencing of the mouse genome. In December 1999, Celera completed the release of a partially assembled Drosophila genome sequence to the public data bank. Celera continues to do scientific analysis in conjunction with the Berkeley Drosophila Genome Project (BDGP) and other collaborators. Celera and its collaborators have discovered a total of 14,000 genes in the genome, many in commercially important protein families, which should prove valuable in developing new therapeutics and insecticides. Celera announced recently that the company has DNA sequence in the Celera database that covers 90 per cent of the human genome. As a result of the extensive sequence coverage of the 23 pairs of human chromosomes and based on statistical analysis, Celera believes that greater than 97 per cent of all human genes are now represented in the Celera database. Celera's DNA sequence is from more than 10 million high quality sequences, generated at Celera in the world's largest DNA data factory. The sequence, developed from randomly selected fragments of all human chromosomes, contains over 5.3 billion base pairs (letters of the human genetic code) at greater than 99 per cent accuracy. The 5.3 billion base pairs represent 2.58 billion base pairs of unique sequence that have been calculated to cover 81 per cent of an estimated genome size of 3.18 billion base pairs. These data, combined with all of the "finished" and "draft" human genome sequence data from the public databases, give Celera coverage of 90 per cent of the human genome. Celera's sequencing was performed on 300 PE Biosystems ABI Prismâ 3700 DNA Analyzers. "The whole genome shotgun technique focuses on sequencing the entire genome at once, allowing for real-time discovery of human genes across the entire genome," said J.Craig Venter, Celera's president and chief scientific officer. "The early phase of sequencing the human genome using the whole genome shotgun process is especially important for gene discovery. We are rapidly coming to an end of that phase. Our statistical analysis and comparison to known genes suggest that greater than 97 per cent of all human genes are represented in our database." Celera began to sequence the human genome on September 8, 1999, using the whole genome shotgun technique that its scientists pioneered in sequencing the first complete genome in 1995 at The Institute for Genomic Research (TIGR). This technique involves randomly shearing the human chromosomes into millions of pieces of 2,000 and 10,000 base pairs in length. The chromosome fragments are inserted into a plasmid vector and propagated in E. coli to produce millions of copies of each fragment. Celera scientists then sequence both ends of each fragment. The millions of sequences representing billions of letters of genetic code are then assembled into the proper order using proprietary genome assembly algorithms and the Celera supercomputer facility, resulting in the reconstruction of the linear sequence of the 23 pairs of human chromosomes. The human genome sequencing effort funded by governments and some public charities around the world is based on sequencing large clones of human DNA in bacterial artificial chromosomes (BAC) using a variation of the shotgun sequencing method. With that approach, approximately 25,000 BAC clones have to be sequenced and their order mapped to reassemble the 23 human chromosomes. There are on average 150,000 letters of human DNA in a BAC. Its "draft" sequence represents most of these base pairs; however the fragments of DNA sequence are largely unordered. By combining the Celera whole genome data with the individual clone "draft" BAC data, Celera plans to order the sequence within each BAC clone and then place the clones in the proper order to construct the genome's sequence. Celera expects to simultaneously and independently assemble the genome with its whole genome assembly algorithms. The combination of these two complementary genome sequencing and assembly approaches greatly reduces the time for Celera to finish the sequence of the human genome. For the next several months Celera plans to continue its full-scale effort on human genome sequencing, with the anticipated addition of approximately two billion base pairs per month. The additional sequences should provide redundant coverage of the chromosome sequences, improve accuracy and aid in the final assembly of the chromosome sequences. When sequencing and scientific analysis of the human genome is completed, the consensus sequence data will be submitted for publication in a scientific journal. These published data will be made freely available to researchers around the world under a non-redistribution agreement. Celera's gene discovery team has identified several thousand new genes that potentially play key roles in cellular communication and the regulation of physiological systems in the human body, including blood pressure, cell growth, and neurotransmission. These are primarily rarely expressed genes and are not represented in the public database, GenBank. These are genes of significant interest to the pharmaceutical industry, since they can be used as the basis of new therapeutic development. Celera has previously reported filing provisional patent applications on newly discovered genes and continues to file these applications on medically relevant gene discoveries. The company intends to file full applications on those medically important discoveries, and has implemented a non-exclusive licensing program to make the intellectual property available to Celera database subscribers.
UK Patents Granted on Dolly The Sheep Technology The Roslin Institute of Scotland announced recently the granting of UK patents that cover critical aspects of the technology used to create Dolly the sheep. The UK patents were granted on 19th January 2000 by the UK Patent Office and cover the use of quiescent cells in nuclear transfer. A Notice of Allowance has also been received from the U.S. Patent Office for a patent application filed to protect this technology in the U.S. These patents originate from applications filed by Roslin Institute on 31st August, 1995. Professor Grahame Bulfield, the Director of Roslin Institute commented: "These patents confirms the novelty of Roslin Institute's cloning technology. They are the first of a series that we expect to be granted over the next year which will reinforce the leading position of our licencees, PPL Therapeutics and Geron Corporation, in the application of cloning technology to develop exciting new therapies for a wide range of debilitating human diseases". He added "The quiescence technology that is covered by these patents was the breakthrough that resulted in the cloning of Dolly. Other research groups have produced cloned sheep, cows, mice and goats and to date, there is no convincing evidence yet published that clones have been produced by nuclear transfer from other than quiescent cells". The UK patents include claims that cover the possible use of the technology in therapeutic cloning of human cells. This is important in the light of the joint recommendation by the UK's Human Fertilisation and Embryology Authority and Human Genetics Advisory Committee in December 1998 that UK law allowing research on human embryos should be amended to add this specific purpose. This recommendation is currently under review by a panel chaired by the Chief Medical Officer of the Department of Health, Dr Liam Donaldson. The UK patents granted are numbered GB 2318578 and GB 2331751 and are jointly owned by the Roslin Institute (www.ri.bbsrc.ac.uk), the Biotechnology and Biological Sciences Research Council (BBSRC) (www.bbsrc.ac.uk) and the Ministry of Agriculture, Fisheries and Food (MAFF) (www.maff.gov.uk). Two licences have been agreed for Roslin Institute's nuclear transfer technology. PPL Therapeutics has an exclusive world-wide licence for uses in production of pharmaceutical proteins in the milk of ruminants and rabbits and for nutraceutical applications. Geron Corporation of Menlo Park, California has an exclusive world-wide licence to all other areas of application as a result of a collaborative research agreement concluded with Roslin Institute in May, 1999. Uses in human reproductive cloning are specifically excluded from this licence. The Bioindustry Association of the UK has produced a document on the mechanics and ethical issues of the patenting process called 'Innovation from Nature'. Copies of this can be downloaded from the BIA website at http://www.bioindustry.org/activities/publications/inf/html The latest edition of Biomednet's HMS Beagle is online. This has a variety of news and views on bioscience issues. http://www.biomednet.com/hmsbeagle Amgen has received approval in the UK for its Neupogen granulocyte colony stimulating factor (C-CSF) for the additional indication of human immunodeficiency virus (HIV) infection. The UK is acting as the reference member state for the European Union's mutual recognition procedure. Source: Biocommerce Abstracts 21 (24) 29.12.99 Aurora Biosciences has signed a three year agreement with Glaxo Wellcome under which Aurora will provide Glaxo Wellcome with access to its ion channel drug discovery technology, including its voltage ion probe reader, voltage sensor dyes and related assay technology. Aurora has also signed a five year agreement with Wyeth-Ayerst Laboratories providing the latter with access to Aurora's technology, assays and instrumentation for ion channel drug discovery. Source: Biocommerce Abstracts 21 (24) 29.12.99 Following Bio-Rad Laboratories' recent purchase of Pasteur Sanofi Diagnostics (PSD), Bio-Rad has engaged the services of Alliance Francaise to provide instruction in French for key managers to encourage communication between staff at the two companies. Source: Biocommerce Abstracts, 21 (24) 29.12.99 DSM Biologics has appointed to its advisory board for recombinant protein production and gene therapy applications, P Gray, R Guttmann, E Keshavarsz-Moore, H Levine and K Hejnaes. Source: Biocommerce Abstracts, 21 (24) 29.12.99 Oxford GlycoSciences Plc has announced a research collaboration with Merck & Co Inc of Whitehouse Station, NG, to apply proteomics in a joint exploratory discovery research program in diabetes. http://www.ogs.com IBM is investing £60m in developing a new supercomputer which it claims will be 500 times as powerful as the world's fastest computers today. The computer, 'Blue Gene', should allow biotechnology scientists to model research puzzles involving human proteins and could speed up the design of new drugs for the pharmaceutical industry. http://www.ibm.com/news/1999/12/06.phtml Keith McCullagh, former Chief Executive of British Biotech, is seeking up to £25 million for a new Internet healthcare business. Dr McCullagh has recently established an Internet business called OnMedica which offers a round-up of medical and biotech news. http://www.onmedica.co.uk Goldman Sachs has brought out an analyst report entitled 'Biotech 2000' featuring British Biotech, Cantab, Celltech Chirscience, Genset, Neurosearch, Peptide Therapeutics, PowderJect, Scotia, Shire Pharmaceuticals, Vanguard Medica. Further information: stephen.mcgarry@hs.com Cambridge Antibody Technology has announced a multidisciplinary strategic alliance
with Searle, the pharmaceutical business of Monsanto http://www.catplc.co.uk/
Novartis has set up a website backing biotechnology. They are giving away free
bumper stickers with "We back biotech!" and a picture of a corn cob. The site
details are: http://www.webackbiotech.com
This is a great idea, and Scott Carpenter has started looking around here to
see how much it would cost to produce a similar sticker here.
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