June 15, 2011 (Vol. 31, No. 12)

Country Positions Itself to Attract Greater Investment and Draw in More Firms

Buildup of the Scottish life science infrastructure should take no one by surprise. From pioneering work on insulin, penicillin, and interferon to the cloning of Dolly the sheep, Scotland has long been a major player on the biomedical stage.

A variety of interested parties—from the U.K. and Scottish governments to the National Health Service to research institutions—have been developing and mobilizing physical and financial resources to attract the kind of investment they feel would allow them to better capitalize on the country’s intellectual prowess, in other words, to be able to do more translational research and spin out and attract more biotech companies.

A key aspect of this is to encourage critical mass. “Good science is all about scientists coming together, interacting, and exchanging ideas,” says Mike Capaldi, Ph.D., commercialization director of the Edinburgh BioQuarter. The Edinburgh area boasts at least eight science parks, including the Easter Bush Research Center—which houses the Roslin Institute, Royal (Dick) School of Veterinary Sciences, and the Scottish Agricultural College—and several business incubators.

Among these is the Edinburgh BioQuarter, located a few kilometers from the city center on what is still mostly sheep pasture. The University of Edinburgh has created several units there, such as the Scottish Center for Regenerative Medicine, the Queens Medical Research Institute, and the Brain and Body Institute, to draw researchers from different disciplines who are working on similar problems, “pull them out of the little departments and little schools dotted around Edinburgh, and bring them to major research institutes,” explains Dr. Capaldi.

A major teaching hospital is on the campus, with another slated to open in 2016, for a total of about 1,300 beds. “Researchers with a medical focus will be able to quickly move into the patient environment,” Dr. Capaldi says.

But it’s not all academics. A three-story bioincubator will begin operations this fall, and there is plenty of land for expansion. The hope is that startups and small biotechs will want to (re-)locate there, and larger ones will see the benefit of expanding to the BioQuarter as well.

Aquila BioMedical plans to be among the Edinburgh BioQuarter bioincubator’s first tenants, harnessing the “leading experts we have here to function as research directors,” says director Howard Marriage, Ph.D. As an advanced preclinical CRO, Aquila is tapping into what Dr. Marriage sees as the emerging business model for the industry—the virtually integrated pharmaceutical company (VIPCO)—in which functions from R&D to sales and distribution will be outsourced.

The company will offer both wet lab and in silico services to help select better, more effective drug candidates by examining and modeling the mechanisms behind the interactions. “Because of the infrastructure that we’re setting up here, we can actually bring in models from other academics and from other companies that are forming here,” Dr. Marriage says.

Initially, Aquila will focus on the molecular mechanisms of multiple sclerosis—a major area of research in Edinburgh—and other T cell-mediated disorders.

In Silico

FIOS Genomics is among several companies spun out of the University of Edinburgh in recent years to provide services to the biotech community.

The CRO makes use of its in-house-developed software tools and high-performance computing platform, which gives it the speed, scalability, and flexibility to analyze large volumes of complex data that are typically generated from the use of next-generation sequencing and gene-expression technologies, explains Gary Rubin, Ph.D., director of operations. But “most importantly, this is linked to the expertise in the company that provides expert analysis and interpretation of the data.”

“So we try to provide the more meaningful, insightful information from the data through data mining, data exploration, and linking that to our own knowledge base in specific therapeutic areas such as oncology, inflammation, and immunology.”

“There is quite a high manual input,” adds Anton Enright, Ph.D., the company’s bioinformatics and technical lead. It draws from both public and internal resources to “attach the key elements to the data and transform it from pure data to actual information, with interpretation on it as well.”

Although FIOS operates purely in silico, it partners with laboratory service providers and CROs to provide wet-lab services as needed.

In Situ Imaging

Ventilated, bed-ridden patients are at great risk for acute lung injury or infection. A portable x-ray machine can tell that there’s something wrong—a shadow on the lung, perhaps—but not what that something is, and subsequent microbiological culture can take awhile. Yet for treatment to be effective, it should be initiated within about 24 hours—otherwise there is about a 60% rate of mortality.

Enter Edinburgh Molecular Imaging (EMI), which was incorporated in March. EMI is developing a system for fluorescent microscopy through a fiber optic cable, which is relatively easy to administer in already intubated patients.

Three types of molecular probes will be used: the first will fluoresce on contact with bacteria, the second differentiates between Gram-negative and Gram-positive bacteria, and the third detects methicillin-resistant Staphylococcus aureus. These can be dispensed in micro doses (subtherapeutic amounts) into the lung and imaged in less than 15 minutes.

These probes should be available for in vivo use in animals within a year. However, “in terms of probes actually coming out as clinical diagnostics, we’re talking about five years’ time,” the company reports.

DNA Vaccines

The big idea behind BigDNA is to let the body produce its own proteins for vaccination. BigDNA’s strategy is to clone an antigen into bacteriophage λ. The phage is used to infect E. coli, which can then be grown up in large quantities. It’s then harvested, purified, and used to inoculate the animal, where it is picked up by monocytes. The monocytes break it down, transcribe the DNA, and express the encoded antigen on their surface.

Unlike a standard protein vaccine, DNA vaccines usually have a greater cellular component as well as an antibody response. “So you get a response that’s more similar to an actual infection than just to the proteins of the vaccine,” says Karen Jervis, Ph.D., the company’s commercial director.

DNA vaccines are also relatively inexpensive and quick to produce—an influenza vaccine could be available within four weeks of identifying the strain, for example, compared to the one-year lead time necessary with today’s technology. And, because the protein coat protects the DNA, the vaccines are also relatively stable at room temperature, obviating the need for a cold transport and storage chain.

BigDNA’s lead product, slated for clinical trials in 2013, codes for the same hepatitis B antigen that has been delivered in millions (if not billions) of inoculations.

“As a consequence, the clinical correlates of protection are extremely well characterized,” Dr. Jervis explains. “It is, therefore, the perfect candidate indication for our first product—what you see in the clinic will be attributable to the vaccine.” Experiments using an early version show a greater response in rabbits after one or two courses than does a three-course regimen of the standard protein vaccine.

BigDNA has benefited from the Scottish government’s commitment to advancement of the biomedical industry. It obtained funding from the Scottish Enterprise, which enabled the commercial potential of its technology to be assessed. Subsequent investment allowed BigDNA to be established at the Roslin Biocentre, where its research is focused on IP acquired from Scotland’s Moredun Research Institute.


Perhaps the most recognizable single name in Scottish biotech is Roslin.

BigDNA is located in the Roslin Biocentre in Roslin, a few kilometers outside of Edinburgh proper. Sheep Dolly, Polly, and Molly were cloned at the Roslin Institute, which moved to a new 500-researcher capacity building this year. The Roslin Foundation is a charity associated with the Roslin Institute and the University of Edinburgh.

Among other endeavors, the Roslin Foundation owns Roslin Cells, the mission of which is to supply undifferentiated stem cell lines for use in therapy, and to facilitate development of stem cell therapies.

It’s important that clinical-grade cells be procured, isolated, manipulated, and stored in ways that researchers and regulators are confident that they’re fit to be put into patients. Roslin Cells is very much about quality control; it assures that consent and procurement of the initial tissue is correct and well documented, and it writes everything down. “There are standard operating procedures for everything we do,” says CEO Aidan Courtney.

Once tissue is procured, Roslin Cells isolates the cells of interest and establishes a population of cells or a cell line that could be the starting material for a therapy.

Courtney makes no pretenses about doing the kind of ground-breaking work that gets reported in high-impact journals. Rather, Roslin Cells’ core competence is the ability to work with academics with an expertise in differentiating cells to a particular lineage—liver or endothelial cells, for example—to reduce theory down to a robust, solid, industrial process. “We’ve got a major GMP cell-processing facility that is embedded in European regulations.”

Later this year Roslin Cells will move its operations to the Scottish Center for Regenerative Medicine, where it will operate seven cleanrooms.

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