Scotland is at the forefront of stem cell research but, with America investing billions of pounds, can we make serious money out of this science?

By Julia Fields, Senior Business Writer
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May 20, 2007
Sunday Herald - Scotland's award-winning independent newspaper
http://www.sundayherald.com/business...is_science.php

WHEN THE governor of Massachusetts pledged earlier this month to make his state "the capital of stem cell research on the planet", one could almost hear the collective sigh ringing across the stem cell laboratories of Scotland. Another day, another billion dollars.

And, indeed, governor Deval Patrick promised to give that magic number over the next 10 years to human embryonic stem cell research. His generosity would match New York State, which is also proposing a $1 billion cash infusion, and at least make it slightly more competitive against California, which plans to stump up $3bn over the next decade.

The commitment puts into context just how competitive the stem cell research field is becoming and invites the question of how exactly the UK, and more specifically Scotland, hopes to remain a world-class contender. In 10 years' time, will we actually see any economic and medical benefits from the millions of pounds worth of investment from our government agencies?

Those involved in the field - from scientists and government officials to investors and businessmen - all believe the answer to those questions is yes; but not in the way many might expect.

Newspaper headlines around the world have focused on the potential for stem cells, the body's master cells that are capable of becoming any kind of tissue, to cure diseases such as Parkinson's, MS and diabetes.

In Scotland, researchers are working in all of these areas. And the Sunday Herald can reveal that two cutting-edge stem cell therapies being researched in Edinburgh - one to regenerate bone and cartilage and the other to repair damage to the cornea of the eye - are about to receive funding to move towards clinical trials. These advancements, combined with the £59m Scottish Centre for Regenerative Medicine, to be developed by the University of Edinburgh and Scottish Enterprise over the next three years, arguably gives this country the edge over almost every other region in the UK.

But according to some of our most respected scientific luminaries, the reality is that we are still likely to see only a small number of treatments enter patient trials in the next decade. The complexity of the science, a shortage of funding and the lengthy trials needed to prove the benefits of therapies to patients means that Scotland's best bet to create wealth out of this scientific field in the short to medium term could very well lie in becoming the stem cell factory of Europe.

Revenues are more likely to be generated from producing clinical-grade stem cells and the various solutions and cultures that make them grow and differentiate to sell to pharmaceutical companies and research institutes.

"What will come out of it is there will be a small number of treatments in 10 years' time. The main thing, in terms of going into practice, could well be that cells will be used for drug discovery," says Ian Wilmut, co-creator of Dolly the sheep and head of the Centre for Regenerative Medicine at Edinburgh university.

"What people tend to do is assume all the benefit will depend on cell therapies, putting cells in people. We think that's overlooking the huge opportunity to study drugs. For example, a huge factor in the differences between people and our response to medicine arises from differences in liver function. To have hepatocytes human liver cells that you could use to screen for toxicity of drugs will be very important."

It doesn't sound particularly sexy, but the benefits could be vast. Big Pharma spends billions of pounds developing new drugs, but these often fail once they are tested in human patients and before they ever get to market. Worse still, surveys have shown that adverse reactions to medicine that actually do make it to the GPs' desk are the fifth most common cause of death in the United States - even when they are taken according to instructions.

"What people have to do now to test drugs is use animals or cells from animals. Just to be able to replace that with human cells is likely to be more accurate and improve the quality of the drugs," Wilmut explains. "It's very likely that the biggest benefit in a 10-year window will be the drug discovery advancements."

The drug discovery services market - reagents, screens and testing technologies - is worth $20bn. If stem cells could account for even a fraction of that, it would still be a very lucrative opportunity. It is in this area that many Scottish companies are banking on generating revenues for the time being.

Dundee-based CXR Biosciences, for instance, was working with Geron and the Roslin Institute to create liver cells out of embryonic stem cells. At the moment, the only source of cells is from cadavers, and the supply is insufficient to meet the demand of the thousands of drug discovery programmes taking place around the world. That particular collaboration has since ended and CXR is in discussions with prospective partners to continue the research with its share of the intellectual property. But according to its chief executive, Tom Shepherd, CXR could potentially double the size of its workforce to near 80 staff if its technology works.

Scottish Biomedical, a Glasgow drug discovery services company, is also attempting to create hepatocytes. And it is so convinced of the commercial potential of stem cell science that it is investing £1.5m (£500,000 of which is coming from the Executive) into a new research initiative to create markers (like light switches) that would help scientists monitor how a stem cell decides to change into a heart or nerve or pancreatic cell. It hopes this knowledge will help it stem cell lines that would have characteristics of a disease, for example, the type of neuron that might appear in a Parkinson's patient - an extremely valuable commodity for pharmaceutical companies.

According to chairman David Dodd, Edinburgh-based Stem Cell Sciences (SCS) is already profiting from a similar commercialisation strategy. The firm, which has operations in Cambridge, Australia, California and Kobe, Japan, is preparing to animal-test therapies for age-related eye disease and spinal cord injuries. But for the time being, it is generating revenues by licensing out its solutions for helping embryonic stem cells grow and change into particular types of cells.

Earlier this year, SCS signed an agreement to provide five mouse stem cell lines (that have been changed into neuron cells) to Philadelphia-based Merck to be used for testing in their drug discovery programmes.

"It was a very big agreement because it was the first time I had seen a company of the stature of Merck not only offer an upfront payment (for the technology) but also offer milestone payments from potential drugs based on these stem cell lines," says Dodd, who has held senior executive positions at some of the largest life sciences companies in the world, including Serologicals, Wyeth and Bristol-Myers Squibb. "It's a very important validation of not just the company, but also for stem cell biology and its application to the future of drug discovery."

These small steps are already producing new jobs in Scotland. SCS employs 26 people in Edinburgh. Cellartis, a Swedish company that has moved to Scotland to create an automated way of producing stem cells, will hire 75 people in the coming years. Although the numbers are small, these kind of jobs come with considerably larger paychecks than many industries.

In the longer term, however, the big money is far more likely to come from breakthrough cures and therapies. Not only could they save national healthcare systems billions by eliminating the need for long-term care, but some analysts estimate that stem cell therapeutics could be worth $10-30bn. But that is likely to be much further in the future than many would like to believe.

Dodd says the promise that cures and life-changing therapies from stem cells could be right around the corner "is the greatest area of hype we have seen in some time". Twenty-five years ago, there was a similar frenzy in the scientific world over the potential for monoclonal antibodies to cure cancer, he points out. "There are drugs hitting the marketplace now, but it took 15 years longer than expected and many of the promises were just hopes and dreams," he says. "Therapies are never developed very quickly. Human biology is extremely complex."

And it is not just the science that moves slowly. There are a host of factors that can get in the way. The ethical implications and the relative infancy of the field have raised all kinds of issues about how research and potential clinical trials are regulated - and by whom.

Scottish Enterprise has put funding towards launching the Roslin Cells Centre, a joint initiative with the Roslin Institute, University of Edinburgh and the Scottish Blood Transfusion Service. The non-profit company, led by Paul de Sousa, will create human stem cell lines from donated eggs and embryos and sell them at a cost-recovery basis in the hope that the lower expense will help young companies and research teams enter the field with new ideas and techniques. Stem cell lines will also be needed for therapies being attempted in trials.

But to gain regulatory approval of drugs or therapies in the future, the stem cells will have to be produced under what is referred to as Good Manufacturing Production (GMP) sterile conditions and standards. The lab rooms have been built. But no protocols actually exist in the UK to officially approve a facility as GMP-ready. In what can only be described as bureaucratic madness, months have passed by while two UK bodies argued over which one was responsible for this task. A new authority is now being set up and it is expected that a temporary inspectorate will be able to certify the labs within the next year. British scientists, however, have complained that such delays potentially give the Americans and Asians a head start in the race to produce and commercialise stem cell therapies.

Funding is also a major stumbling block for any blockbuster cures or treatments to get off the ground in Scotland, and even the UK as a whole. While the British government says it will spend up to £100m on stem cell science this year, the vast majority of that money will be allocated to basic research rather than bringing therapies towards clinical trials. It has yet to release £10m of funding promised for this area. Scottish Enterprise is credited by many for its financial commitment to the field, including setting up a £5m translational fund. But there is a recognition that its resources can only stretch so far.

And many institutional investors and venture capitalists believe the field is simply too much of a gamble at this early stage. In recognition of this problem, the UK Stem Cell Foundation was set up by captains of industry, such as Richard Branson and venture capitalist Chris Evans, to raise capital from high net worth individuals, corporations and government agencies to speed up the transition of stem cell research from the laboratory to clinical trials. To date, the charity has raised more than £20m. But in two years, it has awarded a grant to just one project. It is now about to award money to one project in Edinburgh, and a further three Scottish-led ventures are in the final stages of evaluation. But why has it taken so long?

According to sources, the evaluators are trying to ensure that each project operates to the highest standards. "The reason it takes a long time is that these are human trials and therefore they are under intense scrutiny. They have to operate at the best practice level. In the past, people rushed into the clinic with imperfect models and there were adverse events which set back the industry." The other reason for delays, sources say, is that £10m of the foundation's money is expected to come from the UK government. But that money is being held up by discussions over the conditions under which it should be given out.

But even if some projects secure funding from the foundation, there are many others waiting in a queue. And therapies for more complicated conditions such as MS and spinal cord injuries, particularly those involving embryonic stem cells as opposed to adult stem cells, could take hundreds of millions of pounds just to trial.

Stephen Hammond, chief executive of Scottish Biomedical, remains unconvinced that Scotland - or even the UK as a whole - will have the resources.

"There are great people with great ideas ready to go. Have we got the infrastructure to move that forward? Probably not," he says. "We'll make money in providing technology. We'll make a living on that over the next three to four years. But investors want to back companies that will be able to cure diabetes. Ideas will be bought up and exploited by foreign companies and we'll be buying them back from them in 20 years' time."

It's a depressing prospect. And one that frustrates stem cell pioneers such as John Ansell, a director with the Scottish Stem Cell Network, a body that strives to bring everyone in the field to work together. He, too, has concerns that Scotland, which has all the ingredients to be a major world player, will be pushed to the side by deep-pocketed Americans.

"What we get out of this is entirely dependent on the resources that go into it. We have the people, the ideas, but it's entirely resource-dependent."