Europe: The Hard Cell
by Simon Kent
October 2008
Stem cell research receives official funding from the European Parliament. But the opportunities this presents for EU researchers remain complex and controversial.
Photography by Steve Gschmeissner/Photo Researchers, Inc.
In June 2006 the European Parliament followed the lead of the European Commission and allowed funding from the European Seventh Framework Programme (FP7) to support research projects that involve embryonic or adult stem cells. The decision may seem to indicate a liberal attitude to this controversial area of research, but it does not—nor will it ever—mean carte blanche for researchers in the European Union (EU).
The decision was taken with a significant amount of resistance from some member states—even though the previous framework program already supported this area of research. Moreover, all research of this nature is still subject to licensing and legislation in each EU member country. In other words, regardless of the available cash, what researchers can do differs according to where they are located. Procurement of stem cells from embryos, for example, is not permitted in Austria, Ireland, Lithuania, Poland or the Slovak Republic. In France, Germany and Italy, new stem cell lines can be imported, but not created. Only the United Kingdom and Belgium have laws that actually permit the creation of human embryos for the procurement of embryonic stem cells.
Evidence that the EU’s positive decision on FP7 stem cell funding was not taken lightly comes in the form of a large document published by The European Group on Ethics in Science and New Technologies to the European Commission, concurrent to FP7, advising on the considerations that should be made before granting funds to stem cell-based projects. Central to this advice is that human embryonic stem cells should come only from non-implanted IVF embryos and that alternatives to this form of research should be maximized at all times.
Localized Legislation
The differences in response to stem cell research between member states are dramatic. France, for example, has been proactive, adopting a bioethics law in 2004 that prohibits reproductive and therapeutic cloning as well as detailing the IVF source of embryos favored by the European Group on Ethics. At the same time, the bill created the Agency for Biomedicine, which was charged with patrolling and developing this area of medicine including cell and organ transplantation, reproduction, genetics and embryology. The law came complete with a review date set for 2009.
Across the Channel in May this year, the U.K. Parliament reviewed legislation surrounding this science and made the decision to enable researchers to create animal-human hybrid embryos with strict rules governing their use and development (embryos must not be allowed to grow beyond 14 days). This is useful and practical guidance for researchers concerning what they can and can’t do—and is in stark contrast not only with France, but also Croatia, Romania and Cyprus that have no explicit legislation on this area of research.
Non-Unified Europe
To some extent, the potential for stem cell research in the EU is being compromised by this lack of unified legislation among member states. The differences, driven by ethical, political and religious arguments, have an enormous impact on the location and type of research that can be carried out across Europe and even on the careers of the researchers themselves. In December 2006 the careers section of the journal Science ran an article that described how researchers who wanted experience in the field of human stem cells had to be incredibly mobile in order to find relevant projects with significant resources.
Dr. Nicole zur Nieden, group leader of the Stem Cell Technologies section of the Fraunhofer Institute for Cell Therapy and Immunology in Leipzig, Germany, reports a similar experience. “I did my postdoctoral fellowship in Canada where they are open to stem cell research,” she says. “When I came back to Germany, I was still interested in pursuing this area but it was very tough. As a compromise, we use embryonic stem cells from non-human primates.”
However, zur Nieden says the divergent rules and regulations across Europe further frustrate the work of researchers who may be working with colleagues across the EU. “I coordinated a project last year that had partners located all over Europe,” she says. “We were working on differentiating liver cells from stem cells. There came a point where we wanted to take the research one step further, but in parts of the EU, you could not do anything more. In others parts [of the world], the scientists could take it to the next level. This is very difficult to deal with when you are trying to ensure the research remains a group project.”
Scientific Challenges
However, if the ethical and political landscape presents a challenge to European stem cell researchers, the science itself does not make for an easy sell to investors. Stem cell therapy has the potential to make a difference to some of the most high-profile conditions and diseases. Huntington’s and Parkinson’s disease, cancer, diabetes and heart disease all include stem cell research as one line of investigation into patient treatment. But while offering an effective pull for funds, impatience with results delivered so far can be detrimental to the progression of this new science.
“There is a long way to go from laboratory bench to patient treatment,” says Jamie Levey, chief operating officer of the European Huntington’s Disease Network (EHDN) based in Paris, France. “When a patient or family member sees something achieved in a mouse model, they think they’re going to find a cure very soon,” she says. “It might take eight years to produce anything for patient use—so we need to be very careful to manage expectations.”
Helmuth van Es, Ph.D., owner and CEO of strategic life science industry consultants BioConsilium, in Toulouse, France, believes some companies have disappeared and more will continue to disappear because of the companies’ inability to deliver the science quickly enough. “Stem cell biology is complex, and there are still many unknowns that make it difficult to translate the science into realistic therapeutic applications,” he says. “The expectations will probably be met at some point in time, but the extent of that achievement and the speed at which it happens is nothing like the hype the science has attracted. This has had a negative effect, and consequently investors don’t want to get involved at the same level as before.”
“The slowness of the science has been due to difficulties with transplantation and managing the immune response and safety issues,” says Christine Mummery, Ph.D., professor of developmental biology at Leiden University Medical Center in The Netherlands. “In general, a lot of the trials using adult stem cells have been disappointing.” Indeed, there is even the suggestion that some calls for research and offers of funding are actually out of step with the current position of stem cell research. At the end of the day, there simply aren’t that many researchers ready to take their work to clinical trial, and very often it is precisely that step in which funders are most interested.
“Money is available,” says Dr. Alan Schafer, head of molecular and physiological sciences at The Wellcome Trust in London. “More money is always better, but a problem with this research is that, while, if you double your money you might get double the return, if you increase it fourfold or tenfold, you might not get that same return. We are working with very complicated systems, so simply putting money in doesn’t always help.”
Reflecting the belief that money isn’t everything, The Wellcome Trust has invested heavily in the education and training side of the stem cell discipline, rather than sticking only to supporting ongoing projects. The Wellcome Trust Centre for Stem Cell Research in Cambridge, U.K. has invested £10 million pounds (about US$19.7 million) in its international center of excellence and has linked the center with a doctoral program to improve opportunities for students who want to specialize in this area. “It’s a question of getting the best scientists to work on these projects,” Schafer says. “We want to attract and develop the next generation because this is a new area of practice—and there are a limited number of people working in it.”
Although organizations such as The Wellcome Trust and the EHDN make significant contributions to the stem cell field, Levey is keen to point out that generosity may leave governments with the misconception that stem cell research is adequately supported.
With a high level of resources sourced independently, the local government might decide such research does not require funding from the public purse. “Part of our work is always to try and get local funding for additional activities around the research program,” she says. “Governments should not neglect their responsibility as a primary source of funding for stem cell research.”
Recently there has been a suggestion that stem cell research might be able to break free of its embryonic source altogether, thereby opening itself up to more funding for a less controversial activity. At the center of this move is the use of induced Pluripotent Stem Cells (iPSC). First created in Kyoto, Japan in 2006, these cells appear to have the same nature as embryonic stem cells, but are derived from adult stem cells.
Exciting as iPSCs are, they are still far from widespread in their use or even creation. According to Mummery, at the annual meeting of the International Society for Stem Cell Research in June this year—while many of the scientists present were making attempts—only a handful of attendees had created such cells.
She also notes that human embryonic stem cells will still be required for comparison to ensure the iPSCs are behaving in a consistent and safe manner. “We still don’t know how stable these cells are,” she says. “Will they stay consistent or will they change when we work with them? Are the differentiated cells derived from adult stem cells as stable as those from embryonic stem cells?”
“It is too early to say what the real impact of iPSCs will be,” says Dr. Stephen Minger, senior lecturer in stem cell biology at King’s College in London. “They could be very useful for making disease-specific cell lines, but we simply don’t know how similar they are to embryonic stem cells.”
Steps Forward
Despite the uncertainty and apparent low level of returns in stem cell research, significant steps forward are being made in the EU. Cardiac muscle cells have successfully been grown at Utrecht University Medical Centre and the Hubrecht Laboratory in The Netherlands. Additionally, Swiss scientists at the University of Geneva have made leaps forward in understanding acute lymphoblastic leukemia, promising—at some point in the future—beneficial changes in the treatment of leukemia patients.
“Every little breakthrough, although incremental, is significant,” Minger says. “Things we learn about Parkinson’s disease, using hybrid human ES cell lines, for example, may tell us a lot about how disease operates in the brain or how we can prevent neurodegeneration in some of these cells.”
In the midst of this cutting-edge science, it’s easy to forget that stem cell research is barely six years old. It will need some time to find its feet and move out of what will be seen as the Stone Age of its existence. Interestingly, zur Nieden says that cross-disciplinary—the way in which researchers and scientists are working together in this area—is the most significant accomplishment in stem cell research. “The networking side of the research is extremely valuable,” she says, “Wherever you are working, it is good to be able to share ideas and techniques in order to get more out of this research.”
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