Livestock Biotechnology

Transcription

1 Australian Research in Livestock Biotechnology by Dr. Peter Willadsen Chief Scientist, CSIRO Livestock Industries Australian Agriculture and the Importance of R&D Agriculture remains critical to the Australian economy. Although its direct contribution to Australian GDP has fallen from 4% to 3% over the last two decades, this greatly undervalues its impact. It underpins, for example, the processed food and beverage industry in Australia, the country s largest manufacturing industry, which alone contributes 2.3% to Australia s GDP1. Australian agriculture is strongly export-oriented, accounting for about one-quarter of Australia s merchandise exports in For the larger livestock industries, the average proportion of production exported ranges from a low of just over 50% for dairy products to 98% for wool. In , Asian countries accounted for 50% of our export markets. Within the various agricultural industries, the beef industry accounts for the highest gross value of production of any agricultural sector as well as the highest export earnings, while beef, dairy, wool and sheep are among the seven major contributors to both gross value of production and export earnings. 1 In social terms, outside capital cities and a small number of other large urban centers, the population is largely dependent on agriculture and allied industries, the only other significant contributor being tourism. Agriculture nevertheless faces problems. As a whole, Australia has one of the lowest levels of tariff protection for agriculture in the world. Farm incomes are low and often static or even falling. Key issues for the future are achieving productivity and profitability growth while improving the environmental sustainability of the farming enterprise. Biotech has a role to play in all of these. 796 APBN Vol. 9 No

2 Over the last two to three decades, productivity growth has been steady though higher for plant-based agriculture than for livestock. From , it averaged 3.3% per annum for grains or a total increase of about 240% compared with 30% or less for the dairy, beef and sheep industries. In part, this is attributed to the greater investment in research and development by the grains sector since it is estimated that for agriculture as a whole, R&D has driven 85% of the productivity growth. 1 There is therefore a good argument that for Australia s livestock industries a greater focus on R&D is both justified and essential. Structure and Funding of Livestock Biotech R&D In biotech-related R&D in agriculture, veterinary and environmental sciences totalled A$345 million (US$260.9 million), a third of total biotech-related R&D in Australia. The private sector is significant and continues to grow. Of the 400 dedicated biotech firms in Australia at December 2004, 16% were in agbiotech while for the firms formed in , 20% of the focus was on agriculture. 2 Overall, it is reasonable to assume that about one-third of the total agbiotech effort was expended in livestock research. A number of the new biotech firms focused specifically on the livestock area, for example Veterinary Research Synergies and Vet Biotechnology Ltd whose initial focus is on horses. Agbiotech R&D in Australia is driven overwhelmingly by the public sector with funding from both federal and state governments. The total R&D effort is distributed across a multiplicity of organizations in a complex and multifaceted way. Largest of all is CSIRO Livestock Industries, an organization of 620 staff and approximately 420 scientists with five laboratories across Australia. Embedded within CSIRO Livestock Industries is the Australian Animal Health Laboratory (AAHL), a high security virus containment laboratory targeted at preparedness against exotic livestock disease. AAHL is closely involved with a number of countries in Asia and globally. The Departments of Agriculture of all Australian states also perform research though the commitment to livestock biotech varies from state to state. Complimenting these are the research efforts within universities and other tertiary institutions. Unique to the Australian research landscape are the Cooperative Research Centers or CRCs. These typically involve one or more tertiary institutions, one or more commercial companies or end-user organizations and often CSIRO. CSIRO, created by an act of parliament to assist Australian industry, occupies the middle ground between basic research and research delivery and is a member of approximately two-thirds of all CRCs. A significant number of these have at least part of their research portfolio in the area of livestock biotechnology. For example, new CRCs approved in December 2004 included the Australasian Invasive Animal CRC, the CRC for an Internationally Competitive Pork Industry and the CRC for Beef Genetic Technologies, adding to existing CRCs that have part of their research portfolio in livestock biotechnology, namely the CRC for Australian Sheep Industry, the Australian Poultry CRC, the CRC for Australian Biosecurity: Emerging Infectious Diseases and the CRC for Innovative Dairy Products. The APBN Vol. 9 No

3 funding for these CRCs, like that for CSIRO, the Universities and the State Departments, comes from a mixture of sources, but is dominated by public funding. In livestock biotechnology, the major private funding comes from producer organizations like Meat and Livestock Australia (MLA) or Australian Wool Innovations (AWI). These invest in research through levies on production supplemented by federal funding in a way which intentionally gives these organizations a great deal of leverage in the determination of research objectives. The attitude of livestock industries towards biotechnology, as expressed by these producer organizations, has fluctuated over time but at the moment there is a more concerted effort to channel resources into the development of biotech applications. For example, AWI and the MLA are jointly providing A$30 million (US$22.7 million) over five years to support a coordinated effort in sheep genomics using as research partners CSIRO Livestock Industries, the research arms of the state agriculture departments of Victoria and South Australia, six universities and AgResearch New Zealand. Targets for this research are the genes determining meat quality, wool production and quality, resistance to intestinal parasites and reproduction. The research is supported by an underlying development of core technologies ( Industry Focus and Recent Successes Livestock biotech in Australia focuses principally on the areas of genetic markers, genetic engineering and breeding, anti-microbials, embryo transplantation, diagnostics and therapeutics underpinned by fundamental work in animal genomics. The following recent achievements give a flavor of this effort. The Bovine Genome In 2003 an international consortium led by the United States and involving institutions in Canada, New Zealand and Australia obtained funding for the sequencing of the bovine genome. Australia is represented by CSIRO Livestock Industries. High throughput sequencing was done at the Baylor College of Medicine. Work began in December 2003 and a 6X assembled bovine genome sequence was released in June A second assembly at approximately 8X coverage will be completed by the end of 2005 or early Annotation of the sequence, which is publicly available, will be the result of an international collaboration. After this extremely rapid success, the consortium has embarked on a second stage, the identification of a minimum of 100,000 SNPs to be generated by late Twenty thousand SNPs selected to span the whole of the draft bovine genome are being validated in eight or more breeds of cattle representing all of the major beef and dairy, temperate and tropical production breeds. Livestock Industries is actively engaged in SNP validation in the Brahman breed, a mainstay of the cattle industry in northern Australia and many other tropical parts of the world. Accompanying this effort is a developing consortium working on haplotype mapping of cattle breeds. 798 APBN Vol. 9 No

4 DNA Tests for High Value Genes in Cattle The three major determinants of production efficiency and consumer acceptance in beef are tenderness, retail beef yield and marbling, i.e. the quantity and distribution of intramuscular fat. Although different markets vary in the value they place on these characteristics, they are all important. Unfortunately, although there is a large genetic component to these traits, the traits themselves are complex. Australia currently leads the way in the identification and commercialization of tests for genes responsible for these characteristics and their incorporation into farm breeding programs. This is the result of a typical Australian R&D collaboration. The core resource, DNA from structured breeding herds involving more than 11,000 animals with up to 100 measurements per animal, was developed by the CRC for Cattle and Beef Quality. The fundamental molecular genetics leading to the identification of the DNA markers was performed by CSIRO Livestock Industries and the MLA provided partial funding and support of the research to both the CRC and CSIRO. The markers were commercialized by Genetic Solutions P/L, a Brisbane-based genetic information company that has developed and validated the commercial testing process and now offers these and a genetic advisory service in Australia. The technology is also licensed by Genetic Solutions to the United States where the market is expanding. Diagnostics Emerging and exotic diseases are a constant concern to Australia, in large part because the country is free of many major diseases. Biotech now plays an essential role in the characterization and diagnosis of these agents. Examples of recent success in the identification and diagnosis of new disease agents include the Hendra virus and Australian bat lyssavirus, viruses that caused a small number of human mortalities. Australian R&D assisted with the characterization and diagnosis of the Nipah virus, a previously unrecorded disease that emerged in Malaysia in , killing thousands of pigs and over 100 humans. 3 The virus turned out to be related to but distinct from the Hendra virus. Like all emerging disease situations, the response involved many organizations but the core Australian role was played by AAHL. The laboratory continues its involvement with preparedness for diseases like avian influenza and the severe acute respiratory syndrome (SARS), with major contributions now from the CRC for Australian Biosecurity as well. Examples of commercial livestock diagnostics include Bovigam, a γ- interferon-based assay marketed by Pfizer and developed originally by CSIRO for bovine tuberculosis; an IGF-1 diagnostic as a breeding tool, developed by Primegro and a PCR-based diagnostic for yellowhead virus, a major shrimp pathogen in Asia, developed between institutions in Thailand and CSIRO, then produced and marketed by Farming Intelligence Technology Company in Taiwan. APBN Vol. 9 No

5 Therapeutics Australian involvement in the development of peptide and recombinant vaccines, particularly for veterinary applications, is long standing. Pfizer, through its acquisition of CSL, now markets peptide-based vaccines against boar taint in pigs and for oestrus control in horses. The TickGARD vaccine against the cattle tick was the world s first commercially available, recombinant vaccine against any parasite. It was registered and released commercially in 1994, the result of a collaboration between Biotech Australia (a subsidiary of Hoechst AG) and CSIRO. A very successful recombinant vaccine against the parasite Taenia ovis was registered about the same time, but not finally marketed. Other products have followed: for example, a recombinant vaccine against Pasteurella, licensed to Intervet by CSIRO, a vaccine against infectious bursal disease of poultry licensed to Merial, a recombinant E. coli vaccine from CSL and a vaccine against Eimeria, where intellectual property developed within the University of Technology Sydney has been licensed to ABIC Ltd. Israel. The markets for these vaccines are international. The use of antibiotics in increasing livestock productivity, particularly in intensive systems, is everywhere a matter of concern. An alternative approach showing considerable promise involves the delivery of cytokines in a viral vector. The technology, developed by CSIRO, has been licensed to Vectogen/ Imugene and is currently undergoing further development. Human Livestock Overlap Scientifically, it should not be surprising that advances in the application of veterinary biotechnology should have implications for human medicine and welfare. Nevertheless, the link appears to be underappreciated. Examples from recent research in Australia include the diagnosis and management of zoonotic diseases like the bat lyssavirus, Nipah virus, Hendra virus, SARS and avian influenza. Essentially the same technology as the Bovigam assay, mentioned above, is utilized by the Australian company Cellestis for the FDA-approved Quantiferon-TB Gold test for human tuberculosis. In terms of therapeutics, fowlpox viral vectors developed initially for veterinary application are now being applied for human vaccination, initially in experimental vaccination against AIDS. Technology covering a fowlpox delivery system and co-delivery of cytokines has been licensed by the Australian National University and CSIRO to Virax. Technology of course can readily flow from livestock to human and back again. Betabiotics, a recently formed spinoff developing antimicrobials aimed at a new and ubiquitous bacterial target, arose out of CSIRO s livestock research. Its initial market should be in human therapeutics but, if successful, the technology would be applicable to livestock pathogens as well. 800 APBN Vol. 9 No

6 Governments, Issues and the Regulatory Framework Australian governments not only support research but also contribute in two additional ways to the development of agbiotech. Firstly, both federal and state governments offer a number of schemes typically targeted at early phase commercial development. These complement and sometimes substitute for venture capital investment in the industry. Secondly, the government, through the Office of the Gene Technology Regulator (OGTR), provides a regulatory framework in which biotech can develop. This office supervises the regulatory system governing gene technologies and in particular approval for the intentional release of GMOs. Currently, for example, approval has been granted for intentional release of modified bovine herpesvirus while the use of viral vectors to deliver immunomodulatory agents is under consideration (see For many aspects of agbiotech, public acceptance is not an issue. DNAbased diagnostics, whether for disease or for production characteristics, and the use of recombinant vaccines have been accepted without difficulty. In the area of transgenics in Australia, as elsewhere in the world, the public debate continues. Transgenic sheep and pigs, and cloned sheep and dairy cattle have been produced, but although the research continues, the path to market is not clear. The current situation with plant biotech is indicative of a situation which may arise for livestock biotech in the future. Despite early use and widespread adoption of transgenic cotton and the approval of field trials of transgenic canola in Australia, currently all state governments, with the exception of Queensland, have a moratorium on further release of transgenic crops. There is cautious optimism that this may change in the near future, since good scientific justification for the moratorium is lacking. Nevertheless, the path to market for replication of competent transgenic organisms is currently not clear. APBN Vol. 9 No

7 Delivery of R&D Agbiotech delivers to the livestock industries in diverse ways. Characterization and diagnosis of emerging and exotic diseases is principally the responsibility of government laboratories, the foremost being AAHL. Recombinant vaccine development has resided with major international animal health companies through licensing deals with Australian inventors. In the area of diagnostics and genotyping for parentage or productivity traits, as well as in some highly novel products, startup Australian biotechs are finding their place. Examples for all such commercial strategies have been given above. The number of small Australian agbiotech startups continues to increase. Despite these positive signs, given the strong research base in Australia in livestock biotech and the size of the local livestock industries, it would seem that local commercial development has lagged behind the research capacity. References: 1. Australian Agriculture and Food Sector Stocktake. Department of Agriculture, Fisheries and Forestry, 2005 (see 2. Hopper, K. and Thorburn, L. BioIndustry Review: Australia and New Zealand. Innovation Dynamics Pty Ltd, Chua, K. B., et al. Nipah virus: a recently emergent deadly paramyxovirus. Science 288: (2000). Contact Details: Commonwealth Scientific and Industrial Research Organisation (CSIRO) Livestock Industries Address: Queensland Bioscience Precinct, 306 Carmody Road, St Lucia 4067, Australia Tel: Fax: URL: ndustries&style=divisionfocus 802 APBN Vol. 9 No