Ireland nutures a biotech revolution

Ireland’s biotechnology industry has emerged to become the second largest pharmaceutical manufacturer and exporter after Germany and is now a hotbed of biotech innovation

Ireland’s biotechnology industry has undergone a renaissance in the last few years. Once overshadowed by England, it has emerged to become the second largest pharmaceutical manufacturer and exporter after Germany and, thanks to significant investment from both government and development agencies, is now a hotbed of biotech innovation. Under the National Development Plan (NDP), the Irish government has two notable initiatives, the Programme for Research in Third Level Institutions (PRTLI) and Science Foundation Ireland, which has €648 million set aside for the biotech sector, bringing the total investment from the Irish government so far to over €2.48 billion. Development agencies like Enterprise Ireland and Invest Northern are also setting up well-funded strategies in Ireland to encourage the transfer of research into viable business opportunities and attract overseas pharmaceutical contract research and development.

The Government has pumped millions of pounds into building a solid biotech infrastructure, creating scientific organisations like the Dublin Molecular Medicine Centre (DMMC) and more recently the Proteome Research Centre at the Conway Institute for Biomolecular and Biomedical Research. The Institute was built with approximately €90 million PRTLI grant funding and opened in September 2003. Both organisations serve as important national scientific resources and are equipped with the latest high throughout, state-of-the-art instrumentation. By applying a range of technologies across a variety of collaborative projects, both aim to increase understanding of the pathogenesis and treatment of commonly acquired diseases and eventually identify novel therapeutic targets that will lead to improved patient care.

The identification of these targets and biomarkers, is a fast growing area in biotechnology, as Professor Stephen Pennington, Director of the Proteomics Research Centre, explained: “The DMMC is in the process of building a network for access to patient samples and history, and protein profiling will form the basis of the Protein Research Centre’s analysis of body fluids to identify, characterise and validate novel biomarkers of disease. Ultimately, the long-term goal is to gain a better understanding of the varied events that occur in diseased states and identify drug targets for interventional therapy.”

“For many diseases, for example pancreatic cancer, a diagnosis tends to occur in the advanced stages of the disease and the prognosis is very poor. Clearly, if you could diagnose the disease earlier then the opportunity for intervention would be much greater. Also, clinicians are increasingly asking why some patients do not respond to treatments while others do. Determining the molecular subtypes to stratify subtypes of patients’ diseases would provide an answer.”

“We might find that diagnostic and prognostic markers arise from not only changes in protein expression, but a combination of markers consisting of genomic, proteomic and metabolomic elements,” continued Stephen. “It may well be that the diagnosis of, for example, pancreatic cancer, comes from measuring levels of both different metabolites and proteins in serum. We’ve done a lot of protein expression profile work to identify proteins differentially expressed in pancreatic cancer and are now functionally validating those proteins to see which are responsible for the phenotypic changes seen during the progression of the disease.”

“We want to make proteomics accessible to as many appropriate biomedical research programmes as possible within the Institute, and by bringing up-to-date technologies into the laboratory we ensure there are as many proteomic workflows as possible to select from.”

Sharing knowledge and equipment
In addition to building collaborative partnerships with other research laboratories, it is also important that science organisations commit to creating strong partnerships with industry, including equipment manufacturers whose expertise, until recently, has not been given the appreciation it deserves. All equipment manufacturers welcome the opportunity to design systems that match the needs of the scientific community and will have instruments at the prototype stage of development ready to trial. Often a manufacturer will ask its customers to test new systems for extended periods of time before they are officially launched and this can lead to a significant increase in laboratory productivity, particularly in the case of very sensitive or high throughput instruments.

In Dublin, Orla Sheils, Senior Lecturer in Molecular Pathology at Trinity College, has experienced firsthand how strong links with the industry can reap dividends through her laboratory’s long relationship with Applied Biosystems beta-testing its instruments. “Applied Biosystems is very good at keeping us up-to-date with any new technologies under development and at the moment we are testing one of its new gene expression instruments, the Expression Array System, to try and streamline our profiling experiments. We have been out to its research laboratories in Foster City to see some equipment in action and sometimes if we have a problem with a sample their scientists will analyse it for us. We have a very good working relationship with the Company, in particular a core of five or six people with whom we work very closely.”

Having the money to purchase up-to-date equipment is a big issue for laboratories and the extra money received from the various funding initiatives is a welcome boost to the research community. The budget needed to invest in technology is beyond that of many small- to medium-sized laboratories and having demo equipment to test and the centres of excellence to collaborate with is important. Not only do they get access to all the latest instruments but it also allows them the opportunity to consider working on other application areas and novel research projects.

One organisation in Ireland where this has happened is PROTEOBIO, the Mass Spectrometry Centre for Proteomics and Biotoxin Research which based in the Cork Institute of Technology. PROTEOBIO is world-renowned as a centre of excellence for analytical chemistry and mass spectrometry and has a great deal of expertise in toxins, particularly seafood toxins and food contaminants. Its work is invaluable for the Country’s economy as Ireland exports 98% of its seafood products to other European countries. Through its own projects, and those funded by government agencies, it has recently been able to make substantial investments in new equipment, opening up other avenues of research.

Director of PROTEOBIO, Dr Kevin James, explained: “In 2000 exported shellfish were still being tested using an EU-recommended animal bioassay, but this technique was seriously flawed due to poor selectivity and sensitivity and it led to toxic shellfish products reaching the marketplace. Several incidents of human intoxications resulted in embargos being imposed on Ireland’s shellfish exports to Europe. The Irish Government approached us to develop new, more sensitive mass spectrometry methods to screen the Country’s shellfish for toxins. This and other EU projects sponsored by Enterprise Ireland and the PRTLI led us to invest in new mass spectrometry equipment.”

“One of our most interesting projects at present is looking at the impact these toxins have on human cells in vitro and any change in protein expression that may result. Acting as biomarkers, these could eventually make it easier to distinguish between toxin and bacterial contamination in patients. The high sensitivity of the two LC/MS/MS instruments that we purchased from Applied Biosystems has helped us to develop other methods to determine toxins and metabolites in clinical research samples such as serum, and we have recently started to study mould mycotoxins, which are found in a variety of foodstuffs, including grains, bread, beer and meat products.”

Higher education forges the way forward
A large proportion of the biotech companies in Ireland have originated from higher education facilities and, as these organisations commit more money to supporting technology transfer initiatives, the number will continue to rise. For example, the University of Ulster has set up a Science Research Parks initiative that aims to provide supportive business environments to new companies that have spun out from the University. Four centres have been set up on campus so far; the Synergy e-Business Incubator (SeBI) in Belfast, the Technology and Engineering Innovation Centre (TEIC) in Jordanstown, the Magee Science Research Park in Derry and the Science Innovation Centre (CSIC) in Coleraine. In addition to the increase in university spin-offs, there will also be an influx of companies offering secondary services such as transgenics, medicinal chemistry and GMP biopharmaceutical manufacturing, which most small to medium-sized companies need but may not have the money to implement in-house.

The rapid growth of the biotech industry has stimulated a great deal of interest from international research organisations looking to train their scientists. PROTEOBIO, for example, has found its interest in toxins is shared by the Spanish Universities of Vigo and Oviedo, with whom it has a special affiliation and student and staff exchange programmes. “These universities in Spain have a very good five year undergraduate degree programme in chemistry and biology and many of my PhD graduates come from there,” continued Kevin. “The only downside to Ireland’s economic boom is that any good chemists we produce are highly sought after in the industry so it’s sometimes hard to retain our best graduates”

That will be Ireland’s next challenge.

by Tony Hardware, European Marketing Communications Manager, Applied Biosystems.