Science Feature - November 2009
Tex Med. 2009;105(11):53-56.
By Ken Ortolon
Human embryonic stem cell research didn't stop in Texas when President George W. Bush banned the use of federal funds for most such research in 2001. However, scientists here say the ban had a tremendous negative impact, not just in Texas but also across the nation, on efforts to find new cures using embryonic stem cells.
Margaret Goodell, PhD, director of the Stem Cells and Regenerative Medicine Center at Baylor College of Medicine, says the perception, particularly in Texas, was that the ban made gaining access to embryonic stem cells for research difficult.
"In fact, there was some accessibility to [stems cells for] the research before, but there was a bigger problem with the perception that there was no accessibility," Dr. Goodell said. "And people were even afraid to come into Texas because they thought Texas had a climate that made it particularly difficult to work with embryonic stem cells."
That perception, however, is likely outdated. In March, President Barack Obama lifted the Bush administration's ban on federal funding for embryonic stem cell research. In addition, scientists here in Texas are excited about the prospect of gaining new federal funding for their research.
Some federal money already is flowing into Texas for such research through grants approved as part of the economic stimulus bill passed earlier this year.
Reversing the Ban
The executive order President Obama signed in March reversed a Bush administration policy that frustrated scientists for eight years. The Bush ban limited use of federal funds for research to only 21 embryonic stem cell lines created before the ban.
Researchers complained that those lines were not diverse enough to allow a wide range of research and that many were unusable because they were contaminated with mouse cells.
"There has been a significant amount of question as to how good those cell lines are," said Brian Herman, PhD, vice president for research at The University of Texas Health Science Center at San Antonio. "There were probably about 20 of them initially, and now people think only one or two of those cell lines may be any good to use."
Scientists also say the Bush ban created other obstacles to their research. Some had to set up separate equipment or laboratories to make sure no federal dollars were spent on embryonic stem cell research, even indirectly.
Peter Davies, MD, PhD, executive vice president for research at the UT Health Science Center at Houston, says researchers had to document that no federal funding flowed into experiments on stem cell lines created after the Bush ban took effect. To comply with the ban, UT-Houston set up an embryonic stem cell research oversight committee to review proposed experiments and make sure funding, equipment, and facilities supporting that research were separate from federally funded activities.
"It was a significant bureaucratic exercise to make sure that was done," Dr. Davies said. "And, for the investigators, the need to duplicate equipment and facilities was plenty wasteful."
Dr. Goodell says Baylor researchers chose not to set up separate facilities and equipment. "Most of us here were working with the federally approved lines so we didn't have to jump through those hoops," she said. "But that put us at a disadvantage with regard to some other labs in other parts of the country that did have access to funds or the other kinds of lines."
Dr. Herman says the ban prompted researchers at UT-San Antonio to work with nonhuman embryonic stem cells isolated from baboons, rhesus monkeys, and other nonhuman primates. "The rationale behind that was that these nonhuman primate cells are very close to human cells," he said. "The genomes of the nonhuman primates and humans are almost 99 percent identical."
Dr. Herman called the Bush ban a "very serious setback" for stem cell research. "The number of cell lines at the end of the day that existed prior to the ban that turned out to be useful was very, very small; it was very difficult to get them; and anybody who wanted to work on human embryonic stem cells basically had to create a complete separate infrastructure to do that," he said. "So I think from a number of different viewpoints, it was a tremendous drag on the progress that could have been made, had the restrictions not been in place."
Dr. Davies says the largest impact of the new Obama policy likely will be increased access to hundreds of new cell lines created with private funding over the past several years. Dr. Goodell agrees.
"Certainly from our scientific, biomedical research perspective it will really be helpful for the whole field to have many more of these lines available to work on," she said. "And, I think it could definitely help increase the pace of advances, which we all still think is going to take quite a long time to see real 'cures' from any kind of embryonic stem cells."
Dr. Davies says that impact won't be felt until those cell lines created with private and other nonfederal funds go through a federal registration process.
"There is a process where the federal government is reviewing, vetting those cell lines to make sure they were appropriately collected, registered, and available for use," he said. "The estimates are that there are hundreds of cell lines out there that now will become available to support research into stem cell biology."
Meanwhile, researchers in Texas moved quickly to take advantage of funding included in the American Recovery and Reinvestment Act of 2009 (ARRA), some of which was specifically targeted at stem cell research.
Dr. Davies says UT-Houston submitted more than 300 grant applications for ARRA funds, some of which involved embryonic stem cell research.
"Our researchers have been writing grants like crazy for the last few months," he said. "There were opportunities specifically for embryonic stem cell research activities in the economic stimulus package. The impact in terms of research opportunities is huge."
UT-San Antonio applied for more than $200 million in stimulus funds and received more than two dozen grants.
Dr. Goodell says Baylor researchers also have applied for and received stimulus money, but she is unaware of any grants received specifically for embryonic stem cell research.
Applying the Knowledge
Even though scientists are excited about the opportunities the new Obama policy presents, they recognize that clinical application of stem cell therapies is still a long way off.
"We recognize it is going to take a while to get this to work and to work most effectively," Dr. Davies said. "It's sophisticated cellular technology."
Dr. Goodell says that there are few therapies that have advanced to the point of clinical trials. One of the few clinical trials under way involves therapy for acute spinal cord injuries developed by California-based Geron Corp. According to Dr. Goodell, California got a leg up on the rest of the country because its legislature voted to put state funding into human embryonic stem cell research.
"The state of California put state money into stem cell research, and people flooded that state," she said. "Scientists went there in droves, and companies set up subsidiaries in California in droves. It has had a positive economic impact on that state and, in the long run, we may see more discoveries in the area coming from that state because of the few years' head start they've had on all this."
Ken Ortolon can be reached by telephone at (800) 880-1300, ext. 1392, or (512) 370-1392; by fax at (512) 370-1629; or by e-mail at Ken Ortolon .
Embryonic Stem Cell Research Still Controversial
Despite the lifting of the Bush administration's ban on using federal funds for human embryonic stem cell research, the issue remains controversial.
Immediately following President Obama's executive order lifting the Bush ban, conservatives in Congress criticized the move. House Minority Leader John Boehner (R-Ohio) said President Obama's decision "rolled back important protections for innocent life, further dividing our nation at a time when we need greater unity to tackle the challenges before us."
Senate Minority Leader Mitch McConnell (R-Ky.) said he supports biomedical research, but "I believe the administration would be far better served by directing taxpayer funds to research on nonembryonic stem cells, which is both effective and ethical."
However, physicians and biomedical researchers say human embryonic stem cell research is important because other types of stem cells have not shown as much potential.
In 2004, the Texas Medical Association House of Delegates adopted policy supporting biomedical research on multipotent stem cells, including embryonic, adult, and cord blood stem cells. That policy also supports the use of somatic cell nuclear transfer technology, also known as therapeutic cloning, in biomedical research. That policy, however, opposes the use of somatic cell nuclear transfer technology for the specific purpose of producing a human child.
While there was opposition to that policy among Texas physicians, those who helped draft the policy say it was "absolutely" the right approach.
"Stem cell research continues to be a very crucial aspect of so many different interventions," said Raymond C. Lewandowski, MD, of Corpus Christi, a former member of the TMA Council on Scientific Affairs who was the lead author of a report that led to the House of Delegates policy. "Until a clear alternative to embryonic stem cells becomes available, either through genetic engineering or manipulation of other cells, research is still crucial in getting an understanding of the mechanisms it takes for cells to develop into the various organs and cell lines that we have, and also to play a role in various types of therapeutic interventions currently in trial."
Brian Herman, PhD, vice president of research at The University of Texas at San Antonio, says scientists there understand the ethical issues of working with human embryos.
"Our scientists here think that work using human embryonic stem cells is very important to the potential cure or development of new therapies for a number of different diseases," he said. "I think they supported the TMA position that this was something we should pursue."
Still, some physicians continue to oppose human embryonic stem cell research on grounds that it violates the sanctity of human life. Dr. Lewandowski says he recognizes there are some physicians and scientists "who are so convicted."
"If there were an alternative to use, we would abandon embryonic stem cells and use adult stem cells or cells that are converted somehow," he said. "But as far as I know, that potential hasn't been released in any other cells so far. I think that is what everyone is hoping for, that we'll find those mechanisms or triggers so that we can eventually abandon the use of human embryos and use other mechanisms."
Neurologic, Cardiovascular Diseases Subjects of Texas Research
Can stem cells be used to treat traumatic brain injury, cure heart disease, or repair a compound bone fracture? Those are just a few of the areas in which Texas researchers are testing the potential of both embryonic and adult stem cells to provide new cures or treatments.
Peter Davies, MD, PhD, executive vice president for research at The University of Texas Health Science Center at Houston, says researchers there have begun clinical trials using stem cells to treat both traumatic brain injury and stroke.
A 61-year-old Liberty man became the first patient enrolled in the stroke trial after he was admitted to a Houston hospital after suffering a stroke. Physicians at the UT Medical School at Houston intravenously injected the patient with stem cells derived from his own bone marrow.
A UT-Houston spokesperson says the man's recovery has gone well. He has gone home, but still returns periodically for brain scans, she says.
Sean Savitz, MD, assistant professor of neurology and the study's lead investigator, says animal studies have shown stem cells can enhance healing following a stroke. "We know that stem cells have some kind of guidance system and migrate to the area of injury. They're not making new brain cells, but they may be enhancing the repair processes and reducing inflammatory damage."
The Phase I safety trial, funded with a pilot grant from The National Institutes of Health and support from the Notsew Orm Sands Foundation, plans to enroll nine more patients who have suffered a stroke and can be treated with the stem cell procedure within 24 to 72 hours of initial symptoms.
Dr. Davies says researchers at UT-Houston also are looking at stem cell use in cardiovascular disease, as well as orthopedics.
"Dr. [James] Willerson, our former president, was one of the pioneers in the use of stem cell therapy for heart failure and cardiovascular disease," he said. "There are a number of researchers following up on those initial findings. There also is a lot of interest in the area of orthopedics and the repair of compound, nonunion fracture and bone regeneration. Those are preclinical experiments here, but I think it's an important area of translation that we're seeing."
Baylor College of Medicine researchers also are looking at the area of heart disease and regeneration of tissue following a heart attack, says Margaret Goodell, PhD, director of the Stem Cells and Regenerative Medicine Center there.
Researchers there also are looking at stem cells in the potential treatment of neurologic degenerative diseases, such as Parkinson's disease, as well as using stem cells to generate insulin-producing cells to treat diabetes.
Brian Herman, PhD, vice president for research at UT Health Science Center at San Antonio, says researchers there are looking at the role of stem cells in cancer, specifically how aberrant growth or deregulated growth of stems cells may contribute to the development of cancer phenotypes.
Dr. Herman himself is investigating the role of different proteins in the differentiation of stem cells in bone and muscle.
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