Cooling the German discussion

A unique network that includes philosophers, lawyers and theologians as well as scientists is helping stem cell research in North Rhine-Westphalia to proceed in the face of stiff opposition.

By Cormac Sheridan

Embryonic stem (ES) cells need extrinsic growth signals. ES cells are shown cultured in the presence (left) and absence (right) of the cytokine LIF (leukemia inhibitory factor). LIF maintains the ES cell's key properties of self renewal and pluripotency. Withdrawal of LIF results in increased cell size and flattened morphology and in loss of alkaline phosphatase activity (red staining) which is a marker for pluripotency of ES cells.
Courtesy of Frank Edenhofer, University of Bonn

In 2001, Oliver Brüstle, a prominent German stem cell scientist, and Wolfgang Clement, then prime minister of the state of North Rhine-Westphalia (NRW), caught a plane to Israel. The purpose of the trip was to pay a visit to...

In 2008, Hans Schöler, Director of the Department of Cell and Developmental Biology at the Max Planck Institute for Molecular Biomedicine, in Münster, shared the Robert Koch Prize with Irving Weissman and Shinya Yamanaka for their critical contributions to stem cell biology. Schöler was the first to derive germline cells from murine embryonic stem cells (ESCs), thus confirming their pluripotency, and he has also played an important role in identifying the factors necessary for deriving induced pluripotent stem cells (iPSCs). His recognition marks a coming of age of sorts for stem cell research in Germany and underlines its internationally competitive position. What happened in between these two dates demonstrates how that might not have occurred without a concerted effort of political, scientific and moral leadership.

Vital Clearance

Shortly after the trip to Israel—after much heated political debate and public hostility—Brüstle received clearance to become the first scientist in Germany to work with human ESC (hESC) lines, which he imported from his Israeli collaborator. Around the same time, the state of NRW established Germany's first and only stem cell network, which played a vital role in anchoring the state's fledgling effort and in supporting scientists working in the area. It has also served as a bridge to the wider community, by recruiting philosophers, lawyers, and theologians who study the ethical, legal and sociological dimensions of stem cell research. The latter group includes several nationally prominent figures, such as the philosophers Ludger Honnefelder and Ludwig Siep. From the outset, the network adopted a dual structure to support these two strands of activity. Each working group operates independently, under a separate budget, but participants do engage in regular exchanges. The work of each informs that of the other.

Retrospectively Brüstle observes that the dual structure was a key factor in eliciting political support for stem cell research from Wolfgang Clement and his successors on each side of the political divide. "You need openness and support from the government, and, up to now, the state government has been extremely supportive. Although the political color has changed, that is a continuous attitude which I really appreciate in North Rhine-Westphalia," says Brüstle.

Space for genuine concerns

Perhaps the network's most important contribution is that it has helped to take some of the heat out of the debate. The atmosphere is much calmer now than at the start of the decade. Back then, Brüstle, as the public face of stem cell science in Germany, was bearing the brunt of a highly personalized campaign from militant opponents. His home address was published in a prominent national newspaper (which has since apologized), and he received death threats that necessitated a year-long police security detail. While rational debate with opponents who resort to those tactics is nearly impossible, the network did create a space for debate among scientists and those who harbor genuine concerns arising out of their religious or philosophical positions. However, it does not strive to engineer an artificial consensus where none exists. It rarely adopts a public position on specific issues. "There are so many different views on this," says Schöler. "This is the German discussion." Moreover, what works for Germany may not be appropriate for other countries, he adds. "Many people in Germany don't understand that - it could be different in a different country."

"The state government has been extremely supportive. Although the political color has changed, that is a continuous attitude."

Because of Germany's engagement with eugenics during the Nazi era, public sensitivities toward genetic research are heightened. The legal framework regulating stem cell research is more restrictive than that of many European countries. Generating hESC lines is not permitted in Germany, as the 1991 Embryo Protection Act requires that any procedure involving a human embryo must be of benefit to it. The 2002 Stem Cell Act initially permitted the importation of hESC lines derived before January 1, 2002, however, the cut-off date was extended to May 1, 2007, which eased problems facing German researchers working with international collaborators who favored using newer lines. Even so, access to hESC lines remains tightly controlled. Each individual project has to be cleared in advance by the Berlin-based Robert Koch Institute, which regulates stem cell research in Germany, and the scientific bar is set high.

Only around a dozen research groups throughout the country—four of which are based in NRW—have received permission to work with hESC lines. The state, unlike other regions, has adopted a neutral position on hESC research at the outset. "They recognize that if you want to support stem cell research, it comes in both flavors, adult and embryonic," says Schöler. The authorities in other states took longer to appreciate this, he says. Stem cell research in NRW is probably stronger as a result. "I think there are excellent stem cell research groups all over Germany. I think you have the highest concentration of them here in North Rhine-Westphalia," he says.

Recruitment Psychology
Oliver Brüstle
© J.H. Darchinger

In all, over 30 research groups—located in Aachen, Bielefeld, Bochum, Bonn, Cologne, Düsseldorf, Essen, Münster and Witten—participate in the organization, which encourages collaboration and interaction between its members and which brokers linkages and exchanges with international networks. "It's small. We cannot compare to any of the large international networks, but it's working," says Brüstle, pointing to the growing numbers of attendees at its scientific meetings and the initiation of international exchanges with stem cell networks in other countries. The network has its own annual budget of €1 million, says managing director Ira Herrmann, who coordinates its activities from the NRW Ministry of Innovation, Science, Research and Technology, in Düsseldorf. Around 70 percent of this is spent on research, providing core funding for a small number of groups led by young researchers. It also provides seed money to kick-start collaborative projects between its members.

The network has helped to take some heat out of the stem cell conflict by creating a space for debate among scientists and those who harbor genuine concerns.

Recruitment remains a problem, however. "It's a basic psychological issue," Brüstle says. Researchers want to work in a country with a positive attitude to their work. Schöler concurs. "In Germany, you're bad unless you're shown to be good," he says. "In the US, you're good until you're shown to be bad." Nevertheless, both remain committed to continuing their work in Germany and to building up the stem cell research effort there. Schöler returned to Germany in 2004, after five years at the University of Pennsylvania.

Brüstle, who is director of the Institute of Reconstructive Neurobiology at the University of Bonn and cofounder of Life & Brain, a campus-based translational research center and biotechnology incubator focused on the central nervous system, has received offers to move elsewhere, but he is staying put. "I felt like it would be running away half way through the game," he says. But the game is on—and Germany is playing.

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