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Stem Cell Pioneer

Oliver Bruestle's work prompts new law for German scientists

http://www.the-scientist.com/yr2003/sep/prof1_030908.html

September 8, 2003
By Silvia Sanides
The Scientist Volume 17, Issue 17, 52

It's a day neurobiologist Oliver Bruestle remembers well. He dropped the letter into the mailbox in August, two years ago. Addressed to the German Research Society, Germany's main funding organization for biomedical research, the envelope contained a grant proposal for work on human embryonic stem cells (ESCs), to be imported from Israel.

"I knew this would generate some waves," relates Bruestle, "but I definitely did not count on a tempest of these proportions." His proposal, routine by most academic standards, would spark a public debate about science that is unrivaled in recent German history. Bruestle has become the country's best-known scientist as the media has lavished him with attention, alternately reviling him as a "Dr. Frankenstein" and "profiteer" or celebrating him as a "cell magician" or "missionary" of medicine.

"The battle has left scars, but it was worthwhile," says Bruestle, head of the recently inaugurated Institute for Reconstructive Neurobiology at the University of Bonn. Located in a suburban research park, the institute meets all specifications necessary to further Bruestle's goal of making Germany a top player in developing stem cell technologies that could one day heal brain diseases such as Parkinson. The facilities, which will eventually house 30 researchers, are still awaiting final touches, but Bruestle's supporting actors in the drama of the past two years are already firmly ensconced in their new surroundings: Four stem cell lines that arrived from Israel in January are growing safely in their pink culture medium in petri dishes.

CELL SECURITY

Some extra security measures are necessary to protect the controversial research subjects. Bruestle says he does not intend to keep his work secret, even though police needed to place his family under protection after a newspaper published his private address. "It's in our interest and the interest of science to debate these issues openly with the public, and to engage in a constructive dialogue with our critics," he asserts.

Bruestle has become a savvy advocate for stem cell research; he even invites strident opponents into his lab to give them a first-hand look at his work. Though he cannot convince everyone of its value, he has found that such close encounters blunt some of the sharpest criticism. However, it's not just the opposition from the public or politicians--or the Catholic Church, of which he is a member--that hurts, he says, but the general lack of support from other researchers interested in the field. "It's made my job tougher," he explains, "because the public perception arises that I'm doing some quirky bit of research nobody else is really engaged in."

But, stem cell research is on the rise worldwide, he adds, and from the outset, it's been his aim to create a home for it in Germany. His generally optimistic attitude led him to fight the battle at home instead of accepting one of the numerous invitations to work abroad. "It's Bruestle's great achievement that scientists in Germany are now studying human ESCs," says fellow stem cell researcher Wolfgang-Michael Franz of the University of Munich. "Work with the cells remains highly restricted though, compared to many other countries."

The Embryo Protection Law of 1990 prohibits all experimentation with human embryos. Reasoning that stem cells are not embryos, Bruestle and other research-ers hoped to use a loophole in the law by importing the cells from other countries where their derivation from surplus embryos is legal. The resulting imbroglio cumulated in a televised session of the full German parliament and split the Berlin government. Chancellor Gerhard Schroeder supported imports on a case-by-case basis, but President Johannes Rau reflected widespread public sentiment when he warned the country to move carefully, pointing to the Nazi history of experimenting on humans.

The legislature did indeed move carefully, reaffirming the validity of the Embryo Protection Law in a January 2002 vote, but granting the limited import of stem cells under special circumstances. Taking a cue from the Bush administration, lawmakers stipulated that cell lines must have been created before January 2002. Bruestle's proposal cleared its final legal hurdle last December.

Several other researchers have since put in their own applications for importing stem cells, and two have already been approved. "Of course, the German research community would have preferred a less restrictive decision, but the compromise is widely seen as the only one achievable in today's climate," Bruestle says. Franz agrees, but he finds it especially troubling that the law is based on what he calls a "moral double standard," because it leaves scientists in other countries to do the ethically controversial work that Germans find disturbing.

For now, research prospects are expanding. After years of coaxing mouse ESCs to develop into brain cells, Bruestle's crew is ready to make the jump from mouse to human. His lab has made headlines over the years with studies demonstrating the successful incorporation of stem cell-derived brain cells into various animal models. In a widely cited paper in Science in 1999, his team reported the successful implantation of glial precursor cells, derived from mouse ESCs, into the brains of rats.1 The animals had been genetically altered to exhibit symptoms of a multiple sclerosis-like illness. After treatment, their condition improved markedly.

Such experiments have made the young field of stem cell technology the focus of great expectations. As a physician who worked with patients for two years before dedicating himself to research, Bruestle warns of a danger in promising too much too early. When explaining his goals to the public, he emphasizes the experimental nature of his work and stresses that medical therapies, if any, will most likely not be ready for another decade or so. "Anything else would be unfair to patients," he explains, "and risky for the future of the field."

BENCH RESEARCH

So for the foreseeable future, Bruestle plans to stick to lab work. He hopes to guide his team successfully in an effort to repeat with human stem cells his previous successes with animal cells. Although administrative work takes up a big chunk of his time these days, he still is instrumental in creating a stimulating research environment in his lab.

"His enthusiasm is palpable," says Stefanie Terstegge, a PhD candidate at the institute. Having worked for other researchers in both France and Germany, she praises Bonn's positive atmosphere and her boss's collegial approach. "He fosters the exchange of ideas and supports individual initiatives," she says. It's a leadership style Bruestle learned to cherish during a four-year stint at the National Institutes of Health. Working in Ron McKay's lab at The National Institute of Neurological Disorders and Stroke proved to be such a rewarding experience, Bruestle says, that he decided to import some of the management practices to his own institute. McKay holds his former postdoc in high esteem. "Oliver recognized the importance of [ESC] research while working in my lab," he relates. "I am sure that his clinical training and research skills will lead to many interesting outcomes."

WORK IN PROGRESS

Meanwhile, success breeds more success for Germany's best-known scientist. Cranes dot the skyline above Bonn's research park, as the noises of major construction work invade Bruestle's Institute. A new building rising next door will house the Life and Brain Center. The University of Bonn is building the ¤35 million facility to promote collaborations between academia and industry in neurobiology. Bruestle helped initiate the project. "It's a first of its kind attempt in Germany to unite academia and the private sector under one roof," he explains. "Modeled after US-style technology platforms, we want to bring together basic research, medical applications, and the biotechnology industry."

Perhaps only outspoken people such as Bruestle can make such projects succeed, but also he has been fortunate to be in the right place at the right time. By luck, Bruestle took up residence in Bonn shortly after the German government decided, in the wake of reunification, to move its headquarters back to Berlin. Concerned that the town on the Rhine would turn into a pitiful backwater, local leaders and the past and present governors of the North Rhine-Westphalia province spared no expense in attracting topnotch research and biotechnology. This supportive economic and political climate has even weathered the present downturn in Germany's biotechnology industry, to which Bonn's research community, and Bruestle, in part owe their good fortune.

One would think it's time to relax and enjoy spending time with his wife and four children. He loves to listen to classical music, and he plays the piano and the French horn. But free time is in short supply, says Bruestle wistfully, and the next battle is already approaching. In July, the European Community issued guidelines for human ESC research under the Sixth Research Framework Programme launched in Brussels.

The new Brussels guidelines are less restrictive than the German rules. Heated debates promptly flare up: Should Germany, through its contributions to the Framework Programme, pay for research elsewhere in Europe that would be illegal in Germany? Are German scientists allowed to collaborate with European colleagues who do such research?

Once again, Bruestle and others find themselves in uncharted legal territory. German opponents of human stem cell research meanwhile are trying to use their influence to make the European guidelines as restrictive as Germany's. "We should be liberal enough to be able to support Europe-wide guidelines," says an exasperated Bruestle. "Everything else doesn't have a future." Looks like Bruestle's French horn will stay in its case for the time being.

Silvia Sanides is a freelance writer in London.

1. O. Bruestle et al., "Embryonic stem cell-derived glial precursors: a source of myelinating transplants," Science, 285:650-1, 1999.
 

Copyright © 2003, The Scientist Inc.