Biotech's golden child is still in utero

Like a gold-plated corkscrew, bioinformatics is all about unplugging the data bottleneck that clogs drug R&D pipelines.

Its gold plating comes from the estimated 20 billion dollars in revenues that the global market for bioinformatics is tipped to generate within five years.

Oceans of biological and chemical data are flowing from projects in genomics and proteomics.

Refining this embarrassingly rich lode of untidy data into useful knowledge is where bioinformatics - the use of computers to solve complex biological problems - shines.

Currently, the bioinformatics industry is at the toddler stage on the world scene and "in utero locally," according to Australian bioinformatics identity Prof Simon Easteal.

The tools and services of bioinformatics underpin gene discovery (high-throughput genetic sequencing), gene function (chips and microarrays, proteomics), computer-aided drug design and molecular modelling, drug development (managing clinical trial efficacy data), pharmacogenomics, toxicology studies, and patient data investigations.

For a glimpse of the computing power needed to handle that tidal wave of data, consider US company Celera Genomics.

En route to winning the race to sequence the human genome, Celera had to assemble a computing platform capable of developing 1.7 teraflops of processor grunt. The company also filled a 70-terabyte database that continues to grow in daily leaps of 15 to 20 gigabytes, according to market research firm IDC.

Even those enormous computing requirements will be dwarfed by Celera's future needs as it shifts from genomics to proteomics.

Morphing to the more complex data environment will trigger a 1000-fold jump in Celeras data management and processing requirements in the current 12-month period, company officials estimated.

The commercial implications of such requirements extrapolated across the life sciences sector are the reason computer vendors are watering at the mouth. The dollar value of the bioinformatics market is bracketed by the usual confusing thicket of estimates.

Bioinformatics sales in the US are expected to reach about $A320 million this year, according to market consultants Frost and Sullivan.

Meanwhile, total sales of servers, storage and related services into the biosciences were $4.4 billion in 2000, according to IDC, which forecasts they will grow to $22 billion by 2006.

The bioinformatics market remains a tiny fraction of the life sciences area and falls into six main segments from a vendor perspective: processors, storage, databases, visualisation, application software and services.

Led by IBM, the major IT suppliers showing most interest in addressing the market are Compaq (processors and storage) Sun Microsystems (processors), Oracle Corp (database) and Silicon Graphics Inc (visualisation).

In the software arena, a growing number of companies, both for-profit and non-profit, are developing bioinformatics tools for data capture, management, analysis, mining, and dissemination.

Reportedly more than 40 US companies, mostly small players, are developing and marketing new bioinformatics tools. In Australia only three or four small pure-play bioinformatics companies have appeared, although some biotechs also have bioinformatic offerings. An example is protein analysis specialist Proteome Systems with its own BioinformatIQ web-based platform for storing, for managing and automating proteome data.

Also in the pure-play arena is the Australian National Genomics Information Service (ANGIS), a supplier of online bioinformatics software and services that straddles the line between a commercial and publicly funded operation.

But the bulk of Australia's current bioinformatics activity is carried out in research centres associated with universities or medical institutes.

A snapshot of the institutional activity includes:

• CBIS - The Centre for Bioinformation Science at Australian National University (cbis.anu.edu.au) is headed by Prof Simon Easteal, a geneticist and Prof Sue Wilson, a statistician. The two co-directors symbolise the mix of biological and mathematical expertise, which characterises the centre. The staff of about 10 also deploy software development and programming talents. It is seen as the optimal combination of skills for attacking the genomic and proteomic problems addressed by bioinformatics.
• CBIS focuses on population genomics - both comparative and functional - and high level systems analyses, according to Easteal. "What we are trying to do is provide a strong academic base for the development of bioinformatics."
• WEHI - Another standout group is the bioinformatics division of Melbourne's Walter and Eliza Hall Institute of medical research. It is headed by Prof Terry Speed, an applied statistician and a leading worker in the field of microarrays, which deals with experiments consisting of thousands of tiny sample spots. Like others in the elite echelon of Australian bioinformatics, Speed spends a significant portion of his time overseas - in his case at the University of California at Berkeley. The WEHI bioinformatics unit is in expansion mode. It has 15 staff members and expects to appoint another five before the end of the year, according to acting head Gordon Smyth. It works in the traditional bioinformatics area of gene sequencing but leans toward statistical genetics. The largest group in the unit is dedicated to microarray work while others are focused on linkage analysis and mapping of family trees to locate genes responsible for hereditary diseases. The unit has developed a statistical analysis methodology, which it makes available to external research communities via downloads from its website.
• SUBIT - One of the newest entrants amongst publicly-funded research institutes is Sydney University's Biological and Informatics Technology centre. As part of its larger biotech initiatives, the university is funding SUBIT for a chair of bioinformatics and two lectureships and is aiming for a staff of six. Headed by Prof Tony Larkum, SUBIT is medically oriented, focused on genome and proteome work and drug design with an interest in epidemiology and analysis of defective genes in populations. SUBIT is setting up shared appointments with the university's maths and computer science departments. 1.The cross-fertilisation of skills will allow it to generate algorithms for searching genomics databases, said Larkum.
• ANGIS - The Australian National Genomics Information Service, now 10 years old, is basically an online application service provider of software tools, database access and services for Australian biomedical research communities. It gets about two thirds of its income from 3500 subscribers in 180 institutions (mainly academic) and one-third through government funding. ANGIS provides access to gene sequence databases including both GenBank and SWISSPROT. It offers public domain and licensed commercial software tools for analysing genome data and database searches. Subscribers can log onto ANGIS with their data, use the tools in their own workbench space and store the results on ANGIS server. It also provides off-site help for customers who need to adapt their computer systems for Unix-based software tools. Located at the University of Sydney, ANGIS has a staff of four, including its head, Mike Poidinger. About three years ago a commercial spin-off from ANGIS set up shop in the US, where it evolved into Entigen, a data integration solutions company for biomedical researchers. One of its principal products is the web interface program BioNavigator, originally developed for ANGIS. Entigen recently suffered a funding crisis and has gone into a dormant phase while it seeks a buyer. ANGIS retains rights to the original incarnation of BioNavigator.
• IMB - The Institute for Molecular Bioscience in Queensland boasts a number of bioinformatics heavyweights, including IMB co-director Prof John Mattick, Advanced Computational Modelling Centre director Prof Kevin Burrage and IMB computational biology and bioinformatics head Prof Mark Ragan. The IMB recently scored an Australian first by winning the rights to host the Intelligent Systems in Molecular Biology (ISMB) conference in 2003. The most prestigious event on the bioinformatics calendar, the four-day conference is the first held outside North America or Europe and is expected to attract 1800 delegates. In addition to functioning as a toolset for biologists, bioinformatics has more creative flipside in areas such as computational biology, according to Ragan. "Rather than just supporting wet labs, it can come forward with hypotheses and ask questions in its own right at a different level." There is also the hope by a number of people that "we can use the (bioinformatics) application area of biology to feed back into computer science and learn how to compute better, " he said. Other hubs of growing activity are the Victorian Bioinformatics Consortium, Tasmania's Intelligent Island and an Adelaide grouping.

Small flotilla heads pure-play biotech

The private sector is not well-seeded with bioinformatics activity. Among the small flotilla of pure-play bioinformatics companies on either side of the Tasman are:

• BioLateral - Develops platforms for biologists interested in becoming bioinformatics-capable. BioLateral (www.biolateral.com.au) has a professional training offering, which is "going gangbusters," according to founder and MD Dr Tim Littlejohn, and is also working on a bioinformatics workstation platform in collaboration with IBM and Apple. Littlejohn, founded ANGIS in an earlier incarnation and headed up some of the US entities which were spun out of it. He is currently helping to set up an Australian Bioinformatics Association that will include regional researchers plus industry representatives.
• Reel Two - A software company spun off from the University of Waikato, Reel Two develops and sells data mining software. It has headquarters in Hamilton, New Zealand and San Francisco. It recently signed a three-year, $1 million dollar pact with US company Gene Ed which delivers bio-specific data mining solutions to clients such as AstraZeneca and Pfizer.
• Biogene-e-us - A newly launched West Australian venture (www.biogene-e-us.com) that offers bioinformatic analysis of data submitted by biomedical researchers. Among the services it provides are gene sequence searches, molecular modelling and gene mapping. It was founded by two young molecular genetics graduates of Curtin University, Rachael Duff and Tracey Wilkinson.
• Desert Scientific Software - Its first product, Proasis2, (www.desertsci.com/Proasis2/) is a web-based protein structure database and visualisation toolset aimed at computational chemists rather than biologists. Founder and chief scientist, Neil Taylor, has a doctorate in computational chemistry and worked in the research labs of global pharmaceutical companies in the UK and the US before returning to Sydney to launch his own company. His client list includes AstraZeneca in Sweden, Roche in Switzerland, Vertex in the US and Glaxo Smith-Kline in the UK.

Vendors race for position

If there is a race to sign up strategic partnership arrangements with bioinformatics businesses in the region, IBM is sitting in pole position. Last November it forged a global alliance with Sydney's Proteome Systems and five months before that signed an agreement with Physiome Systems, a company based in biological modelling technology developed at the University of Auckland.

IBM's strategy involves partnering with application providers rather than writing bioinformatics applications itself.

The company is in the process of building up a team to manage its life sciences business in Asia Pacific. Eddie Clunies-Ross, healthcare manager for IBM Australia said the effort is "just ramping up" in Australia.

Of 11 executives being recruited for the team, three will be posted in Australia, including one PhD, Clunies-Ross said.

Compaq is also beating the bioinformatics bushes in hopes of flushing out revenues. A supplier to the ANU supercomputer centre (and of Celera's processing grunt) Compaq hopes to leverage those credentials into a slice of the processor-hungry bioinformatics business.

Other major vendors appear less active in Australia. SGI, for example, has sold its visualisation systems to many biotech businesses but the company can't yet point to any local alliances of the type forged by IBM.