Cell Block

Missouri scientists fear embryonic research may remain embryonic

embryonic stem-cell research

Stacked in trim rows along a bank of south-facing windows, the petri dishes at Divergence Inc.'s Creve Coeur laboratory house the potential to insulate future crops from roundworms, deadly parasites that every year destroy an estimated 7 to 9 billion dollars' worth of domestic plants. Each dish holds a soybean root system. By exposing the roots to roundworms, researchers hope to identify genes essential to the parasitic worm's existence.

"What we want to do is find a way to shut down the function of that particular gene," explains Divergence chief executive officer Derek Rapp. "That would lead to the killing of that worm in a way that is not dangerous to the environment or the plant."

With 23 employees and a potentially effective — and lucrative — product, Divergence is a case study in how small biotech firms can benefit from close proximity to large research institutions. Many of the company's researchers hail from nearby Washington University, Monsanto and Saint Louis University.

Divergence is also one of nine companies housed at the Nidus Center for Scientific Enterprise, a nonprofit plant- and life-sciences incubator on Monsanto's well-tended Creve Coeur campus. Funded in large part by the Monsanto Fund, the Nidus Center furnishes start-ups with well-appointed laboratories, offices and communal use of machines that would otherwise be out of reach for the fledgling firms.

"I understand those machines cost a half-million dollars each," says Rapp, marveling at a pair of massive stainless-steel sterilizing machines. "The Nidus Center allows us to focus on the work we've set out to do as a company, rather than the infrastructural stuff that is really a hassle."

For many life-sciences proponents in the St. Louis region, companies like Divergence represent not only the great hope for a pest-free agricultural future, but also a key to the economic regeneration of the region.

An unlikely contender, St. Louis now competes with Boston and the San Francisco Bay Area to attract ever more researchers and start-up firms. City boosters hope that developments like Cortex One at the corner of Forest Park Parkway and Boyle Avenue will become an anchor in an emerging 173-acre "biotech neighborhood" planned to cultivate a homegrown biotech industry. There's also a lot of money at stake: Each year, Washington University brings home more than $400 million in federal research grants. There are an estimated 187 plant- and life-science enterprises in the region whose workers earn roughly $63,000 per year, according to a 2002 study conducted by the Battelle Memorial Institute, a nonprofit scientific research trust. Additionally, the Bureau of Labor Statistics reports that there are more than 80,000 regional workers employed in the biosciences sector, a broad category including researchers, doctors and entrepreneurs.

"St. Louis is a major center for biomedical research and plant-science research," says physician and former Washington University Chancellor William Danforth. "The life sciences are going to be very important in the future, and we should be a part of it."

One major obstacle, however, stands in the way: the Missouri anti-abortion lobby and its muscular opposition to embryonic stem-cell research.

"Right to Life will not sit silent whenever you're killing a human embryo," says Susan Klein, legislative liaison for Missouri Right to Life. "There's no reason for us to sacrifice the protection of human life in order to advance our economy."

Using a technique called somatic cell nuclear transfer, scientists have developed the ability to replace the nucleus of embryonic cells with those of mature cells. The technique is alluring to researchers because embryonic stem cells can mature into any type of cell, a quality scientists say could eventually lead to therapies and cures for now-incurable diseases like multiple sclerosis and Alzheimer's.

"This holds the greatest promise of any technique that I've come across," says Steven Teitelbaum, Messing professor of pathology and immunology at Washington University. "We should be moving forward on all fronts."

Opponents of the research, though, consider the collection of embryonic cells used in the research to be a developing human embryo, and say the cells should therefore be accorded the rights and privileges of person.

"Embryonic stem-cell research is a stepping stone for reproductive cloning," maintains Klein. "We do not oppose cures for diseases. We do oppose embryonic stem-cell research: the creation and killing of one human life for another."

The issue has proved a political maelstrom in Jefferson City, as it has in legislative hallways across the country. Republican state senator Matt Bartle has repeatedly introduced legislation that would criminalize both embryonic stem-cell research and any cure derived from the technique. At the same time, Governor Matt Blunt has infuriated pro-life supporters with his repeated pledge to veto any legislation banning stem-cell research.

With the backing of Washington University and the Kansas City-based Stowers Institute for Medical Research, among others, the Coalition for Lifesaving Cures has meanwhile launched an initiative campaign for a constitutional amendment that would ban human cloning in the state while protecting embryonic stem-cell research.

While Missouri wrestles with the issue, other states have moved in a decidedly pro-research direction. California has earmarked $3 billion in state funds to support stem-cell research, and Illinois governor Rod Blagojevich recently signed an executive order freeing up $10 million in funding to lure researchers. Last August the Illinois governor sent letters to 30 Missouri researchers inviting them to resettle across the Mississippi.

"If Missouri became a place that was not friendly to science, where you can't do cutting-edge research, then the best and the brightest just aren't going to come here," says Donn Rubin, executive director of the Coalition for Plant and Life Sciences and chairman of the Missouri Coalition for Lifesaving Cures.

"Investors aren't going to want to come here. Life-sciences companies and investors are going to go to California, or Boston — or even Illinois. We're going to lose all those opportunities."

William Neaves, president and CEO of Kansas City's Stowers Institute, says his organization has already suffered fallout from the political battle over stem-cell research.

"For more than two years, the Stowers Institute has been trying to recruit leading scientists in the field of somatic cell nuclear transfer using human cells," writes Neaves in an e-mail. "Unfortunately, the threat of criminalization has made it impossible for us to convince these scientists to consider moving to Missouri."

Founded by Jim and Virginia Stowers, their eponymous Institute currently has a $2 billion endowment, making it the second-largest such endowment in the country. Opened in 2000, the 600,000-square-foot facility is located on a ten-acre campus in the heart of Kansas City. When fully occupied, the facility will employ 600 people. Importantly, Neaves says, the Institute is also funded to expand by another 600,000-square-foot facility each decade in perpetuity.

"A second facility in Kansas City would entail a $300 million construction project that would yield another 600 permanent jobs upon completion," Neaves explains. "But future expansions of the Institute will only be built in a jurisdiction that welcomes research with early stem cells."

Closer to home, scientists at Washington University say that the pending threat to criminalize embryonic stem-cell research threatens their recruiting abilities in all areas of science.

"Stem-cell research is not an isolated area of research; it's a tool just like any other area of research," contends Washington University's Teitelbaum. "We are the most collaborative institution I know, and if I've had any success as a scientist it is not because of me, it is because of my colleagues who have these specific areas of expertise."

Teitelbaum adds that if the state passes legislation restricting embryonic stem-cell research, all Washington University scientists will be denied a critical area of research, prompting bright young scientists across all disciplines to settle elsewhere.

"Our university in toto ranks in the top ten, but all of this depends upon our ability to recruit the best faculty," says Teitelbaum, a genetics researcher credited with one of the first major breakthroughs in adult stem-cell therapy. "If you can't recruit, you can't remain competitive. This is not just rumor: I know for a fact that these issues are brought up presently by potential recruits. They want to know if they're going to be restricted in what they do if they come here."

For Senator Matt Bartle, however, the potential of life-saving cures, the loss of area jobs and university prestige pale in comparison to what he sees as his duty to protect the unborn.

"This is very simply big business trying to push through a constitutional provision that will allow them to do whatever they please," says Bartle. "It's the same old tired argument: Look at how much money we can make. Well, you know what? If we were to undertake experiments on our prison population that might lead to medical advances, it might lead to jobs in the state of Missouri, but does that justify it? No."

Back at the Nidus Center, Divergence's Derek Rapp points to a microscope in his company's sunny, beaker-filled laboratory. At 10x magnification, the C. elegans roundworm is an undulating s-curve of translucent grace. A close genetic match of their parasitic cousins, C. elegans allow researchers to easily identify target genes in their crop-destroying relatives. And though Divergence does not conduct stem-cell research (there are only a handful of researchers in the state currently studying human embryonic stem cells), the issue is vitally important to the company.

"We've been able to assemble a really strong team here," he says. "Having the presence of Monsanto, the Danforth Plant Science Center and Washington University really helps us do the work that we do.

"But if we start to see an abandonment of science on the part of the state, and that leads to people abandoning the state to do their research, then we'd have to think twice about staying here."

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