Cell Division

Georgia debates stem cell research

James Trussell was 37 in 2003, when he was diagnosed with Parkinson’s disease, but he’d been experiencing the symptoms for several years – the rigidity in his body, the tremors in his hands. Because he was young, and it’s an affliction that typically attacks people over 50, Trussell’s doctors took some time to rule everything else out. Then the neurologist prescribed medicine to treat the symptoms of Parkinson’s.

“He told me, ‘If it works, you have Parkinson’s,’” Trussell says. “The only real way to find out for sure is to have an autopsy, and I’m not quite ready for that.”

He’s quite ready for a cure, though. Trussell and more than a million other Americans are living with Parkinson’s, a progressive, chronic neurological disorder caused by the death of dopamine-producing brain cells, which control movement. Currently there is no cure, and no way to prevent it or detect its onset.

There is hope, Trussell and many others say, in embryonic stem cell research. But even as scientists make breakthroughs in the lab that could lead to cures for devastating diseases, and clinical trials for treatments derived from stem cells move forward, it remains the subject of a national dialogue over ethics – sincere questions of when human life begins – and is shrouded in political gamesmanship, especially in Georgia, where some state leaders want to limit new research.

“That’s something I just don’t understand. It’s mind boggling to me,” says Trussell, the Georgia state coordinator for the Parkinson’s Action Network and co-founder of the Northwest Georgia Parkinson’s Disease Association. “Embryonic stem cell research offers the best chance to find a cure – not just for Parkinson’s but for many illnesses.”

It’s a debate fraught with irony. Georgia has some of the nation’s leading researchers in the area of embryonic stem cells, scientists recruited and paid for by the state as eminent scholars; and state leadership has identified the life sciences as a strategic industry of interest.

And yet, many of Georgia’s elected officials, including Gov. Sonny Perdue, have made it clear that they do not want new research in embryonic stem cells happening in Georgia, even as federal restrictions were lifted by President Barack Obama.

“We want Georgia to be a leader in scientific research, but we do not believe embryos should be destroyed in the process,” says State Sen. Don Thomas, a doctor who runs a family practice in Dalton, and who helped sponsor SB 169, which restricts stem cell research on grounds that it protects an embryo’s right to life. “We can get as much value out of adult stem cells as we can out of embryonic stem cells.”

More value, says Dan Becker, president of Georgia Right to Life. Patients counting on treatments and cures derived from embryonic stem cells are “placing their hope in a false hope. Destructive embryonic stem cell research hasn’t produced significant improvement in the treatment of disease, but there have been significant advances with adult stem cells.”

SB 169 (which does not limit research on adult stem cells, or the existing embryonic stem cell lines approved during the Bush administration) passed in the Senate and will be considered by the House in the next session (following hearings by the House Science and Technology Committee this fall).

Some opponents of the bill claim it was a political knee-jerk reaction to President Obama’s lifting of restrictions on federal funding for embryonic stem cell research. Others say the bill criminalizes embryonic stem cell research and sends a clear message.

“This tells the rest of the nation and the world that Georgia is anti-science,” says Charlie Craig, president of Georgia BIO, which lobbied on behalf of the biotech industry, which it represents, against the bill, along with university scientists and a number of patients’ rights groups.

“If Georgia restricts science that is considered legal and ethical by the federal government and the rest of the world, it creates the perception that we’re not friendly toward life sciences research, and it ignores patients and their families and it kind of dismisses their pain and suffering.

“We believe the general assembly and the governor should not outlaw research, over politics, that can benefit millions of people.”

For David Hess, who chairs the Medical College of Georgia’s neurology department and is advancing research in the area of adult stem cells, it isn’t a political question – he isn’t trying to curry favor with a religious conservative voting block (though he has addressed the legislature on behalf of representatives who oppose embryonic stem cell research).

“I have personally and ethically always had qualms about embryonic stem cell research, and have avoided working with them,” says Hess, co-investigator in a study supported by $6 million in National Institutes of Health (NIH) grants to explore long-term benefits of stem-cell therapy (using adult stem cells), including new therapies for adult stroke and cerebral palsy in children. Clinical trials of treatments are about two years away, Hess says.

Induced Potential

Stem cells are cells that have the potential to develop into different cell types – how many depends on whether they are pluripotent (which can morph into virtually any cell type in the body) or multipotent (which give rise to a small number of different cell types). Scientists are studying the potential of these cellular “repair kits” with the hopes of developing treatments and cures for diseases and conditions, such as Parkinson’s, diabetes, Alzheimer’s and spinal injuries.

Human embryonic stem cells (hESCs) are pluripotent, and therefore considered to have greater developmental potential. These ESCs can be obtained from fertilized eggs that are left over from in vitro fertilization (IVF), or prepared cloned early-stage embryos (therapeutic cloning), called blastocysts.

The religious opposition to ESC research centers on the question of when human life begins, because these days-old embryos are ultimately destroyed; and some people believe these several hundred cells that form a blastocyst have a soul.

This particular area within the field of regenerative medicine is fairly young – the first ESC lines were derived in 1998. No miracle cures have emerged yet, a fact that opponents of ESC research frequently use as ammunition.

“There have never been any successful treatments of any human disease with embryonic stem cells, whereas there have been many with adult stem cells,” notes James E. Carroll, chief of the MCG Section of Pediatric Neurology and a co-investigator in the stem cell study, whose research focuses on cerebral palsy.

“We don’t do embryonic stem cells. It’s an ethical choice. And I think it’s becoming a moot point.”

It’s moot, he says, because of the recent discoveries involving induced pluripotent stem cells (iPS cells), which are pluripotent cells drived from non-pluripotent cells, mainly adult cells. The first iPS cells from humans were produced in 2007. Since then, there have been advances leading to discoveries that counter, somewhat, the iPS cells’ tendency to trigger cancer-causing genes.

“This is a major breakthrough,” says MCG’s Dr. Hess. “Induced pluripotent cells make embryonic stem cells almost irrelevant.”

University of Georgia professor and entrepreneur Steve Stice, a pioneer in stem cell research, works with embryonic stem cells, iPS cells and adult stem cells in his Athens lab.

“You’re looking for the best cell type that will help somebody in the end,” Stice says. “We need to be aware of the moral and ethical issues, but the jury is still very much out on iPS cells. They look very much like embryonic stem cells, but we’re not sure they can do all the things that the embryonic stem cells can do. A lot of very smart people are working on that.

“But there isn’t a one-size-fits-all situation.”

The iPS cells versus embryonic stem cells issue is sort of a chicken and egg situation – without initial research on the existing embrynoic stem cell lines, there wouldn’t have been research that produced iPS cells.

“Induced pluripotent cells are a great success story, but it’s owed wholly to the fact that we had a starting basis in embryonic stem cells,” says Todd McDevitt, a Georgia Tech scientist who directs stem cell technology research in his lab and focuses most of his attention on ES cells. “Comparative studies are a strong reason why embryonic stem cells have already been important and why they will continue to be important.”

Soon, the argument that ES cells haven’t produced a successful treatment in humans could be moot. Geron Corporation (California) received approval from the U.S. Food and Drug Administration (FDA) earlier this year to begin the world’s first clinical trials of hESC-based therapy in humans, in this case to treat patients with acute spinal cord injury.

For Georgia Tech professor Bob Nerem, research needs to move forward in all areas.

“At some point we will know about what makes the most sense from a patient point of view,” says Nerem, director of both the Parker H. Petit Institute for Bioengineering and Bioscience at Tech, and the Georgia Tech-Emory Collabora-tion for Regenerative Medicine (GTEC).

Nerem also is a leader in a movement to support additional research in Georgia, an effort that gave rise to the Georgia Stem Cell Initiative (GSCI) in 2007. With more than 175 members across the state, the GSCI is a partnership of university researchers, industry, public officials and other community leaders who want to advance stem cell research.

“We should be working to provide patients in Georgia access to the most advanced therapies and treatments, including those that are derived from embryonic stem cells,” Nerem says. “Unfortunately, our elected leadership doesn’t seem to get that. And they’re sending signals to the rest of the country, and internationally, that you’d better be careful about making a bio-investment in Georgia.”

Political Alchemy

The 2009 legislative session produced several victories for right-to-life advocates, potential setbacks for ES cell research, and a few raised eyebrows. For example, HB 388 – the nation’s first embryo adoption bill – was passed and went into law in July. It allows for the adoption of even a single zygote. Proponents, such as Becker, claim it offers an alternative to the destruction of unused embryos at IVF clinics.

Meanwhile, SB 169 cleared the Senate floor and awaits House consideration. The bill’s author, David Shafer, a Republican from Duluth (who is gearing up to run for lieutenant governor) did not respond to repeated efforts to contact him, but State Rep. Amos Amerson (R-Dahlonega), who chairs the House Science & Technology Committee, says he will conduct hearings about SB 169 later this month, or in early October.

Amerson wants to learn more about the divisive issues surrounding embryonic stem cell research.

“I want to know everyone’s reasons for why they support or why they oppose this kind of research,” Amerson says. “To me, the right-to-life doesn’t stop at birth. My personal feeling is that we should be doing the research necessary to treat and cure the children who have been born, and give them a chance to grow up.

“If these stem cells are coming from frozen embryos that will be thrown out, I don’t understand the problem.”

Dan Becker leads an organization that has a huge problem with that. Georgia Right to Life stood solidly behind the legislators who pushed through HB 388, and Becker is optimistic that SB 169 will eventually work its way into the law books.

“We have high hopes that the House leadership will be receptive and open to a bill that would restrict some of the more heinous aspects of medical science and technology,” Becker says. “The destruction of human life for research purposes is not something the American people view as acceptable.”

But in July, the NIH released its new guidelines for funding em-bryonic stem cell research, which follows President Obama’s executive order lifting a ban on research. The Bush Administration limited federal funding to the 21 stem cell lines that were in existence as of August 2001. The recently adopted rules allow the use of new stem cell lines derived from IVF procedures, as well as the existing stem cell lines.

“Among scientists, there is a lot of hope that things will improve, that they can once again push out the research frontier,” says Aaron Levine, assistant professor in the School of Public Policy at Georgia Tech, and author of Cloning: A Beginner’s Guide. Levine’s research focuses on the impact of ethical controversy on scientific research.

The past eight years, he says, national policy on stem cell research was defined by President Bush’s personal beliefs.

“Clearly, President Bush’s ethics translated into policy,” Levine says. “One of the results of this was, a number of states began to support stem cell research. Their thinking was, ‘This is important research, we may really improve human health and benefit patients struggling with incurable disease.’”

California, Connecticut, Maryland, New Jersey and Illinois were among the states contributing large sums of taxpayer dollars to fund research, particularly research that was not being funded by the federal government.

“Georgia is an interesting place, because we have some topnotch scientists, Stice and others, who really are at the forefront of the field. But Georgia is a state where the legislature has had some furious questions about this research, and has attempted to place restrictions on it,” Levine says. “It’s an environment where, if you’re a scientist, you might feel a bit nervous.”

In May, Atlanta hosted the annual BIO International Convention. The world’s largest gathering of biotech professionals came to town, and state boosters hoped to show them that Georgia should be taken seriously as a nurturing environment for the life sciences.

“We hoped that the convention would wake people up to the fact that the rest of the world is moving forward in biotech, and Georgia needs to be a leader,” says Georgia BIO’s Charlie Craig.

One of the guest speakers at BIO International was former North Carolina Governor Jim Hunt, who is credited with fostering the growth of the biotech industry in his state. North Carolina, bolstered by its universities and Research Triangle, now is one of the national leaders in the biotech industry and research.

“Obviously, I have strong feelings, and I think we ought to be fully engaged in stem cell research,” Hunt says. “It has the potential to save lives and improve the quality of life for so many people, and we should make every effort to use embryonic stem cells that otherwise would be thrown away.

“At the same time, this is a complex issue and we should be talking about it in a way that respects differing opinions.”

But for a young scientist like Todd McDevitt, whose lab at Georgia Tech has attracted some $2 million in federal funds and employs 10 other researchers, a differing opinion that has the potential to criminalize his work forces him to consider other options.

McDevitt, 34, is a member of the GSCI steering committee (along with Nerem and Stice, among others) and is a rising star in his field. In July he was considering an offer from another institution in another state.

“One of the attractive things is, they have an environment that is extremely supportive of stem cell research, and I can’t predict what will happen with the political landscape here in Georgia,” says McDevitt, who regrets that his scientific research could be affected by outside factors like the whims of political ambition.

“Today it’s one way, tomorrow it could be another way. It could get worse, and Georgia [would] not be a fruitful place to do research and build the career I want. It’s taken me five years to get this lab up and running. I’m still at the start of my career, but I have to consider my long-term options.”