Stem cells on trial: Fate of Stanford’s new stem cell lines in limbo as lawsuit delays funds
Eric Chiao helped create Stanford’s two embryonic stem cell lines, but lack of funds may end his work.
Julie Baker
For Eric Chiao, PhD, the money made available by Proposition 71 represents more than a theoretical boost to stem cell research in California—it's the difference between continuing a research project he considers vital and finding a new job.
With Prop. 71 grant money Chiao could continue developing new embryonic stem cell lines, analyze those lines and begin to understand how stem cells grow into new cell types. If the funds remain in legal limbo, he'll have to put into storage the two cell populations he has isolated—the first and only two lines derived so far at Stanford—and walk away.
"Right now the legal situation with Prop. 71 is the real wrench in the system," said Chiao, who is a research associate working with Julie Baker, PhD, assistant professor of genetics.
In the 2004 election, Proposition 71 passed with a 61 percent vote creating the California Institute for Regenerative Medicine, or CIRM. This organization has roughly $300 million per year to fund stem cell research in California. But the money has been tied up in a legal battle over the constitutionality of the initiative. The trial that will determine the CIRM's fate begins on Feb. 27.
Stem cell research has been widely touted as the route to cures for diabetes, Parkinson's disease and a long list of other currently uncurable disorders. However, the restricted number of human embryonic stem cell lines that President George W. Bush has OK'd for federal research dollars may not be ideal for treating these diseases. Some of the lines are genetically unstable, and each population of cells seems to have a different affinity for forming diverse cells of the body.
"Why is that? No one knows yet," Chiao said. "Do we have the best cells for treating diabetes yet? Or spinal cord injuries? Will one cell line be optimal for all applications? We don't know." The only way to find out, he explained, is to make more cell lines and then identify the best way of growing and maintaining the cells for different applications.
Chiao had been working in Baker's lab as a postdoctoral fellow when he and Baker got the idea to begin creating new stem cell lines. Because the pair can't isolate or study these new embryonic stem cells with federal money, they needed private funding for the work and had to find a way to study the cells using labs and equipment that are completely free of federal funds. That's a tall order in a world where most equipment is purchased through grants from the National Institutes of Health and most lab space only stays afloat with support from federal funds.
Chiao and Baker secured money through the dean's office last year and then found a small, unused laboratory, which they furnished with the bare minimum of research equipment. The idea was for this money to fund two years of work until a more substantial CIRM grant would kick in and allow them to scale up their operation. Where most labs are overrun with microscopes, solutions, computers and various and sundry equipment, this lab practically carries an echo.
In that barren environment, Chiao and research assistant Muriel Kmet have managed to grow two populations of cells from 20 6-day-old embryos donated from Stanford's in vitro fertilization clinic. About half of these balls of roughly 200 cells was either malformed or contained chromosomal abnormalities and could not be implanted in a woman. These embryos would have been thrown out if Chiao weren't available to take them. The other half was frozen embryos donated by couples who had completed IVF treatment.
Chiao now has two goals. One is to keep isolating more human embryonic stem cells as the IVF embryos become available. The other is to study the cells he already has to make sure they behave like proper stem cells, forming all types of cells in the body and using genes that are normally active in embryonic stem cells. The experiments are easy, the logistics are not.
"In order to do an experiment that any lab could do in two days we have six months ahead of us," Baker said.
One problem is equipment. The spartan lab where Chiao works doesn't contain the necessary tools to study the cells. In her main lab, Baker has that equipment in spades, but it was all purchased with federal grants and can't be used to study newly created stem cell lines.
"I could buy the equipment with our current grant, but then I can't pay my salary," Chiao said. Both his salary and Kmet's come from the dean's funds. Similarly, he could pay to have the cells analyzed by a private lab, but that once again brings up the pesky problem of his paycheck. Plus, Chiao would rather spend what money he has trying to create more cell lines out of new embryos when they come in.
"Because the embryos would be thrown away I almost feel like I have a moral responsibility to do this work," he said.
Chiao pointed out that creating new cell lines and freezing them doesn't move the group any closer to studying the cells or making them available to other researchers. For that, they need to analyze the cells and—the gold standard for all biomedical research—publish their findings. "Publishing is critical to show that we have an efficient operation," Baker said.
For Baker, publishing is important for career reasons as well. As a junior faculty member, her continued success at Stanford depends on publishing her work. A few vials of cells sitting in a liquid nitrogen tank won't impress the committee that decides her career fate.
The problems Chiao and Baker face are the same ones slowing the development of new stem cell lines—and research using those cells—across California, where researchers have jumped into the field to chase CIRM money and the promise of medical advances. For the moment, those researchers can go in one of three directions: They can take federal money to work with suboptimal stem cell lines that can't be used in human therapies; they can scrape together private funds and work with newer cell lines under severely limiting conditions or they can abandon the field.
Ideally, Chiao hopes several labs will brave the funding waters and work on developing new stem cell lines. "We're really just starting to know the best way to isolate and grow the cells," he said.
The likelihood of developing effective ways of working with the finicky cells goes up if more people are tackling the problem. What's more, one goal is to develop embryonic stem cell lines from in vitro embryos with genetic mutations that cause diseases such as cystic fibrosis or muscular dystrophy. Developing those lines requires many labs that are able to take the embryos when they become available.
"I don't think there will ever be a time when we can say we have enough embryonic stem cell lines," Chiao said. Keeping a steady supply of the cells for future therapies will require efficient ways of growing up the new populations. It also requires experienced scientists such as Chiao weathering the funding storm and staying in the field. If he and others like him leave stem cell research due to lack of funds, they take their knowledge with them.
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