Stem Cells: The Changing Legal Environment
By Anna Stolley Persky
In 1998 Dr. James A. Thomson isolated stem cells from human embryos, a development hailed as a momentous breakthrough for medical research. The problem: to get the cells, the embryos had to be destroyed.
Since then, the issue of human embryonic stem cell research has divided the country. Opponents say destroying human embryos is an unjustifiable act of murder. Supporters describe embryonic stem cell research as a powerful, new study tool that could result in finding cures for complex human diseases.
In 2001 President George W. Bush plunged his administration into the debate by allowing federal funding for stem cell research, but limiting it to already existing stem cell lines. At the time, Bush said there were enough lines available for important research to continue without the destruction of any new embryos. As it turns out, only 21 stem cell lines are usable for basic research, according to the National Institutes of Health (NIH), the primary federal agency for conducting and supporting medical research.
Embryonic stem cell research has yet to find a cure for Parkinson’s disease, Alzheimer’s, or any other disorder. Some scientists argue that a federal funding drought has stalled research development. NIH projected spending an estimated $203 million for nonembryonic human stem cell research in 2009 and significantly less—$41 million—for research involving the human embryonic stem cell lines. The overall numbers starting in 2001 reflect a similar disparity: $1.3 billion versus $174 million.
“The result of Bush’s decision is that NIH, the greatest engine of scientific research in the history of man, has remained largely on the sidelines for the past eight years,” says Bernard Siegel, executive director of the Wellington, Florida-based Genetics Policy Institute, a leading promoter and defender of stem cell research and other cutting-edge medical research targeting cures.
While President-Elect Barack Obama has vowed to lift the ban on federal funding, pro life advocates argue that tremendous discoveries in stem cell research from other sources, such as umbilical cord blood and teeth, eclipse the need for studies involving embryos.
“Putting money into research using embryos is sinking time and effort into a method that has completely failed and destroys human life,” says Dorinda Bordlee, executive director and senior counsel of Bioethics Defense Fund, a bioethics law and policy organization based in Scottsdale, Arizona.
Despite political opposition, human embryonic stem cell research continues to be funded. Where the federal government has pulled back, researchers are finding other financial sources.
States such as California and Massachusetts have passed laws authorizing human embryonic stem cell research and providing billions of dollars in grants. Other states, such as Arkansas, Indiana, and Louisiana, have passed laws forbidding research on embryos.
Some bioethicists and scientists complain that the United States lacks nationwide ethical guidelines for conducting research and obtaining embryos. The problem, they say, is that human embryonic stem cell research is being conducted under a confusing web of state regulations, private policies, and suggested guidelines from the National Academy of Sciences (NAS), which advises the nation on engineering, medicine, science, and technology.
“There’s been no coherent national regulatory strategy based upon scientific and ethical principles,” says Larry Goldstein, professor in the Department of Cellular and Molecular Medicine and director of the Stem Cell Program at the University of California, San Diego. “What we have is a patchwork of ad hoc solutions by states. That’s bad if you have a disease that could be helped by the research, bad for the economy, and bad for the nation.”
John Edward Porter, a former U.S. congressman who now represents research institutions, does not mince words, either.
“The failure of the Bush administration to provide strong funding for embryonic stem cell research has put the growing competition overseas in the lead in this area,” says Porter, a partner at Hogan & Hartson LLP.
Meanwhile, scientists who want to conduct studies using embryos increasingly decide where to work based upon the laws of the state where a university or laboratory is located.
“It’s basically jurisdictional shopping for scientists,” says Sean Tipton, a founding board member of the Coalition for the Advancement of Medical Research (CAMR) and director of public affairs for the American Society for Reproductive Medicine. “Clearly if you want to work in embryonic stem cell research, you are not going to work in a state where that is illegal. You end up going to a state like California, where laws provide money and infrastructure, resulting in top-notch facilities and the ability to recruit good scientists.”
As this issue of Washington Lawyer went to press, Obama’s transition team has indicated he is considering an executive order to reverse Bush’s restrictions on federal funding for embryonic stem cell research. Assuming Obama issues an executive order, NIH is expected to quickly put out proposed guidelines.
“The guidelines would be binding for anyone who wants to use NIH funding for human embryonic stem cell research in their laboratories,” says Story Landis, head of the NIH Stem Cell Task Force. “Presumably people would want to follow these guidelines no matter what their source of funding.”
Core of the Debate
The debate over research using embryos has, at its core, something very important—the enormous potential of the human stem cell as a tool for further discoveries.
Stem cells are starter cells found in every organ, with the capacity to grow into adult tissue. Embryonic stem cells are derived from the inner mass of an early stage embryo, also called a blastocyst. Human embryos reach the blastocyst stage between four and five days following fertilization.
Embryonic stem cells are pluripotent, which means they can develop into any kind of cell or tissue in the body. Many scientists believe embryonic stem cells could one day be used to treat diseases and generate replacement tissue for damaged organs. “Embryonic stem cells are simply better and more powerful than anything else we’ve found,” Tipton says. “Scientists are trying to reverse engineer the embryo to understand how it works and what gives it its special powers. To understand it, you have to examine it, and you have to do experiments with it. Some of these experiments may involve its destruction. You’re never going to figure out how a car works if you’re never allowed to look under the hood.”
However, not all scientists believe the embryo is the answer.
“The public has been led erroneously to believe that this is going to be an area of research likely to bring forward cures in the short term,” says Maureen Condic, an associate professor at the University of Utah’s Department of Neurobiology and Anatomy. “That’s completely false. Not only do these cells make tumors, they are genetically unstable and fairly rapidly convert into cancer cells. This is a really big problem.”
Still, others believe the destruction of human embryos is an untenable price to pay for any kind of scientific goal.
“We’re talking about human life here,” Bordlee says. “This is a deeply important moral issue to our society and to those who believe that human life is not a commodity.”
That feeling aside, the majority of Americans favor human embryonic stem cell research, according to numerous nationwide polls conducted in recent years.
Since Thomson’s momentous discovery in 1998, stem cell research has developed rapidly. In August 2006 Advanced Cell Technology (ACT), a U.S.-based biotechnology company, announced it had discovered how to make a stem cell line without destroying the embryo used in the process. Three months later, ACT clarified that the research proved human stem cell lines can be created from a single cell removed from a multiple-cell embryo; however, “none of the biopsied embryos were allowed to develop in culture.”
In 2007 Thomson, working at his laboratory at the University of Wisconsin-Madison, and Shinya Yamanaka at Kyoto University in Japan, discovered how to reprogram skin cells to become pluripotent stem cells. The process involves a reprogramming technique that adds a cocktail of four genetic factors to human skin cells, resulting in what is called “induced pluripotent stem cells.”
“This is a breakthrough of giant magnitude. It doesn’t involve eggs. It doesn’t involve embryos. The problem is that while this is hugely promising, it is years out before we will be able to use it,” Siegel says. “Human embryonic stem cells are still the gold standard for researchers.”
Also in 2007, researchers engineered adult stem cells derived from human umbilical cord blood to produce insulin. In the past year, there have been even more discoveries—Japanese scientists said they figured out how to create stem cells from wisdom teeth.
In November Japanese researchers said they had created functioning human brain tissues from embryonic stem cells.
On the other hand, scientists at the Harvard Stem Cell Institute discovered how to transform one type of fully developed adult cell directly into another inside a living animal. The process, described as “direct reprogramming,” involves pinpointing molecular switches that can convert common cells in the pancreas into insulin-producing cells.
Ultimately, researchers say, this process could result in a method to reprogram the cells of patients suffering from diseases and other medical problems. Although the Harvard experiment involved mice, scientists have said they are optimistic the approach could work with human beings.
Pro life advocates insist many of these developments indicate that embryonic stem cell research is no longer necessary.
“Science is actually solving the moral dilemma, and that’s good news for both the ethical questions and scientific progress,” Bordlee says. “Why continue to create and destroy human life when there are other methods out there that make the same kind of cells without the use of cloning, embryos, or human eggs?”
But advocates of embryonic stem cell research say there is no reason to cut off a potentially promising area of study.
“We don’t believe you should artificially close off avenues of research because you never know where your next breakthrough will occur,” says Peter Farnham, director of public affairs for the American Society for Biochemistry and Molecular Biology in Bethesda, Maryland. “The other scientific developments are not far along enough to even remotely substitute for the potential of using embryonic research.”
The same advocates say that while an embryo must be “treated with respect,” it is not “off-limits for research.”
“The human embryo is a special kind of tissue, but it’s a tissue nonetheless,” says Michael Werner, president of The Werner Group, a biotechnology consulting firm in Washington, D.C. “It’s not a person, and it does not have constitutional rights.”
Limited Federal Funding
Two years before Thomson’s 1998 breakthrough, researchers in Scotland announced they had cloned Dolly, the sheep. The process they used—somatic cell nuclear transfer—involves taking the nucleus of an adult cell, transferring it into an unfertilized egg cell, and then stimulating it to grow.
In 2001 publicly traded ACT said its researchers cloned the first early-stage human embryos using the same process. As science has developed, so has the level of concern among some religious organizations and activist groups. Since the late 1990s, the self-described right-to-life movement has pressed for federal and state restrictions on cloning and the destruction of embryos.
In 1993 President Bill Clinton signed the National Institutes of Health Revitalization Act, which gave NIH the authority to fund human embryonic research for the first time. In 1994 an NIH panel recommended that research using spare embryos from fertility clinics receives federal funding.
But Congress addressed the issue next in the Dickey-Wicker Amendment, a rider attached to an appropriations bill for the Department of Health and Human Services. Renewed each year by Congress, Dickey-Wicker bans the use of federal funds for any experiment in which a human embryo is created or destroyed.
In 2000 the Clinton administration endorsed new NIH guidelines permitting funding for research using embryonic stem cell lines gathered by privately funded scientists and then transferred to the NIH Human Embryonic Stem Cell Registry. (In 2007 it was renamed the NIH Human Pluripotent Stem Cell Registry.)
By the time the new guidelines were published, Clinton was close to leaving office, and a new president had taken the helm. How Bush would handle the issue of human embryonic stem cell research was a much-debated topic. Then, in a nationwide address on August 9, 2001, Bush authorized federal funding for the first time—but only on existing stem lines. At the time, he claimed there were “more than 60 genetically diverse stem cell lines” available for use.
“When Bush signed the executive order, he laid the groundwork for tension between parts of the scientific community and the administration,” says Robert Gropp, director of public policy at the Washington, D.C.-based American Institute of Biological Sciences. “The science community thought Bush was too optimistic about the number of usable stem cell lines, and this created concern. Scientists also like to work without a lot of restrictions, and were concerned that this was the beginning of a troubling trend.”
Most of the stem cell lines quickly were deemed unusable.
“There are 21 lines eligible for federal funding, but they have all been exposed to nonhuman cells or products,” says Landis, head of the NIH Stem Cell Task Force. “They are perfectly good for doing basic biology research, but you may not be able to use them for clinical applications in people.”
Since his 2001 announcement, Bush has twice vetoed a bill lifting his restrictions on human embryonic stem cell research. In 2007 he coupled his veto with an executive order to encourage research into alternative methods of obtaining pluripotent stem cell lines.
Meanwhile, some in Congress have been trying to establish national guidelines for ethical stem cell research.
In 2008 Rep. Diana DeGette (D–Colo.) introduced legislation to increase federal ethical oversight of stem cell research. DeGette’s bill emphasized the need for a new oversight body within NIH that would be responsible for monitoring all stem cell research in the United States, regardless of the source of funding. DeGette has urged Obama to adopt portions of the bill, including an ethics review, as part of his administration’s commitment to funding embryonic stem cell research.
“People are shocked when they learn that in this country there really are no overall guidelines that are used,” DeGette says. “We’ve got to have some sort of overarching federal ethical oversight.”
Since 2001 states have struggled with their approach to embryonic stem cell research. State legislatures throughout the country debated the topic—with an array of results.
In January 2004 New Jersey was the first state to legislate funds for embryonic stem cell research, appropriating $10 million in state grants. But it was California that caught the country’s attention. In November 2004 California voters passed a bond measure that devoted $3 billion to stem cell experiments. Proposition 71 set up the California Institute for Regenerative Medicine (CIRM), governed by a 29-member board. CIRM is empowered to fund research using embryonic stem cells.
“California’s move totally changed the political landscape,” Werner says. “Everyone around the country started to say, ‘Whoa, maybe we don’t have to wait until federal policy changes.’”
The effort, however, quickly became entangled in litigation over the constitutionality of the new law. Opponents claimed that CIRM suffered from built-in conflicts of interest and violated the California constitutional requirement of state supervision. In 2007 a unanimous state appeals court panel upheld the law in a 58-page ruling.
The First District Court of Appeal in San Francisco said Proposition 71 “suffers from no constitutional or other legal infirmity” and that litigation had “interfered with implementation for more than two years.” The California Supreme Court declined to review the case.
Advocates of the program say they expect it to bring existing biotech firms into the area and stimulate the creation of new companies.
In 2006 voters in Missouri approved an initiative to change the state constitution to protect embryonic stem cell research. The amendment allows for research to produce embryonic stem cells, but bans cloning to produce a human baby. However, the constitutional amendment does not provide any tax dollars for research.
Other states followed, including Connecticut, Illinois, Massachusetts, New York, and Wisconsin. But some states, such as Arkansas, Indiana, Louisiana, North Dakota, and South Dakota, have banned some or all embryonic stem cell research.
States that authorize funding for embryonic stem cell research address ethical oversight in different ways. California, Connecticut, New Jersey, and New York require the research to be reviewed by oversight committees. Massachusetts, meanwhile, requires researchers to identify any university policies or protocols that apply to the project and to state how they are addressed.
In Maryland, the state legislature created the Maryland Stem Cell Commission to distribute research grants. The state requires that scientists share with other scientists stem cell lines developed using Maryland public funds.
Most recently, in November 2008, Michigan voters approved an amendment to the state constitution allowing researchers to harvest stem cells from embryos left over from fertility treatments.
“Clearly there are some states that are trying to position themselves as friendly environments for the biotech industry,” says CAMR’s Tipton.
“Some states have been very encouraging,” says Areta Kupchyk, a partner with Reed Smith LLP who represents several biotechnology companies with stem cell-related products. “But to the extent that states have had the primary role of regulating embryonic stem cell research, companies and research institutions have been subject to their individual regulatory frameworks.”
‘Legal Horror Show’
Advocates of embryonic stem cell research say they are grateful some states have jumped in to help with funding, but find that the “patchwork approach” creates a great deal of confusion. “It makes doing science much more complicated than it need be and has discouraged people from engaging in this area as fully as they might,” Landis says.
The NAS has published its own nonbinding ethical standards for conducting the research, which most universities adopt. Committees at each institution where research takes place provide additional oversight. The guidelines most recently were updated in September 2008.
Scientists say they have been worried about repercussions if they accidentally merge aspects of a federally funded project with a separate study involving embryos. Therefore, researchers have set up careful accounting systems and clearly separate their laboratories to ensure that any studies on embryos using private or state funds are kept completely apart from those utilizing federal funds.
Janet L. Dolgin, a health care law professor at Hofstra Law School, describes the confusion as a “legal horror show.”
“Researchers at institutions end up trying to follow not just their own rules, but a mix of federal and state rules, too,” Dolgin says. “And then there are questions of conflicting state laws when, for example, two research facilities decide to join up for a project. Which state law should they follow?”
With the confusion over state regulation comes another problem—fertility patients with excess embryos who do not have an easy path to donate for research.
For Californians, donating unused embryos is somewhat simple, thanks to a dedicated tissue bank at the University of California, San Francisco. But patients in other states that do not fund stem cell research often are not able to donate.
“Some [in vitro fertilization (IVF)] clinics in states that ban embryonic research see it as a real hassle to move an embryo to another state,” says Arthur L. Caplan, chair of the Department of Medical Ethics at the University of Pennsylvania. “So your ability to donate depends very much upon what state you are in.”
A 2003 study by the RAND Corporation estimated that nearly 400,000 embryos have been frozen and stored since the late 1970s. However, it is unclear today how many embryos are stored at the nation’s 450 fertility clinics. Some IVF clinics are concerned about the appearance of impropriety or the legality of mentioning donation, so they keep silent on the matter, Caplan says. Other fertility clinics, such as Boston IVF, have a system for providing excess embryos to researchers.
“IVF clinics follow individual policies they have set for themselves, and there’s no federal or state oversight,” says Caplan, who thinks Congress should intervene and ensure an ethical system for providing research institutions with embryos.
Critics say embryo banks that cater to stem cell researchers could end up encouraging doctors to produce even more embryos than are needed. Equally concerning to pro life advocates is the possibility of scientists cloning embryos to create the amount they need.
“This is the ultimate reduction of a human life to a commodity,” says Richard M. Doerflinger, deputy director of the Secretariat for Pro-Life Activities of the U.S. Conference of Catholic Bishops. “The idea of creating life simply to destroy it is very disturbing.”
Farnham, of Bethesda’s American Society for Biochemistry and Molecular Biology, counters that scientists find it disturbing “to think of thousands of people desperately in need of life-saving therapies who might not receive them because of unnecessary restrictions on the creation and use of embryonic stem cells.”
Another issue in the mix: What standards should the Food and Drug Administration (FDA) use when reviewing embryonic stem cell-based products? Geron Corporation of Menlo Park, California, recently filed the first Investigational New Drug application for an embryonic stem cell-based product. The FDA’s Cellular, Tissue and Gene Therapies Advisory Committee held a public meeting to discuss how to ensure the safety of products based upon embryonic stem cells.
At the meeting, CAMR President Amy Rick asked the FDA not to apply an extra layer of standards on embryonic stem cell products simply because the technology is controversial.
“Scientists should assess these products based upon the science, not the controversy or the politics,” Rick says. “The FDA’s role is significant, but it’s not to answer some of the more complicated questions involved in the ethical and political debate.”
Another area of developing law concerns the patenting of human embryonic stem cell lines. The Wisconsin Alumni Research Foundation (WARF) found itself at the center of a media controversy when the Public Patent Foundation of New York and the Foundation for Taxpayer and Consumer Rights challenged several key human embryonic stem cell patents. In 2008 the U.S. Patent and Trademark Office upheld several of WARF’s patents.
“Patent disputes early in a new technology are not unusual, and they tend to work themselves out through litigation, negotiation, licensing arrangements, and other resolution mechanisms,” says Werner of The Werner Group biotechnology consulting firm. “That will be the case for stem cells as well.”
Ron Kamis, a specialist in biotech-nology patents, says the Patent Office “doesn’t take an ethical policy stand” on patent applications for human embryonic stem cells.
“They treat them like any other biotechnology patent,” says Kamis, a partner at Arent Fox LLP.
Congress, at this point, has not intervened to prevent the patenting of human embryonic stem cells.
“There is no regulatory scheme within the patent laws that precludes a company from patenting human embryonic stem cells, or cell lines, or other biological entities that otherwise satisfy the requirements for patentability,” says Patrick A. Doody, a partner at Goodwin Procter LLP specializing in patent law.
What’s the Future?
Advocates of embryonic stem cell research worry that the United States is trailing other countries such as Israel and the United Kingdom when it comes to research development.
“The absence of a good national policy has had a negative impact on our competitiveness in this field,” says Goldstein, the University of California, San Diego professor. “When we’re desperately worried about our economy, it seems to be a bad time not to be investing vigorously and at a national level in such an important area.”
However, pro life advocates say the notion that the United States is falling behind in embryonic stem cell research is a myth. Additionally, they say that our country’s policy should continue to emphasize other areas of research that already have produced exciting results without the moral dilemmas of studies involving the destruction of embryos.
“Every dollar that is spent on embryonic stem cell research is a dollar not spent on research that is currently benefiting patients, such as cord blood stem cell research or bone marrow stem cell research,” says Condic, the University of Utah professor.
If Obama lifts Bush’s ban on federal funding for human embryonic stem cell research within the first few days of his administration, NIH officials predict a significant increase in grant proposals for experiments using human embryos.
Kupchyk, the Reed Smith partner, also predicts “there will be a huge sigh of relief in the medical and scientific community” once the ban is lifted.
“There are many people in that community who believe in the potential of stem cell research and want to see how far it can go,” she says.
NIH is expected to quickly propose guidelines on cell line derivations and research protocols and embryo collection. These guidelines are expected to establish whether federal funding applies to lines from embryos created specifically for reproduction, or all new cell lines.
Among the other issues the guidelines might address are whether IVF clinics and embryo banks could receive payment for providing embryos to researchers, what constitutes informed consent, and who can collect the embryos and in what manner. NIH also could tackle the topic of egg collection for somatic cell nuclear transfer. In total, the guidelines are expected to address many of the same issues already included in the NAS report.
Clearly, the notion of lifting Bush’s limitations on federal funding is upsetting to those who have fought against research on embryos.
“Tragic,” says Mathew D. Staver, dean of Liberty University School of Law in Lynchburg, Virginia, and founder of Liberty Counsel, a nonprofit organization devoted to advancing religious freedom and the sanctity of human life. “This will force the American public to fund the creation of human life and research on human life. It will create a culture of death.”
Advocates on both sides say their fight is far from over—both in the states and Congress. Proponents of the controversial research want to remove the restrictions of the Dickey-Wicker Amendment.
“Yes, this is a new dawn, but there are still roadblocks,” says Siegel, the Genetics Policy Institute executive director. “If we can move that aside, it’s the next step to get the federal government and NIH fully engaged.”
Meanwhile, Bordlee of Bioethics Defense Fund reminds state legislators that “they still retain their ability to enact bans on destructive human embryo research.”
And with the economic downturn, it remains to be seen how much states will want to continue funding research and what the budget will be for NIH.
“It’s clear that we need to dramatically increase the NIH budget. We are going to have fight to do that,” Colorado representative DeGette says. “The federal government needs to step up.”
 California Family Bioethics Council v. California Institute for Regenerative Medicine, 55 Cal. Rptr. 3d 272 (Ct. App. 2007).
Anna Stolley Persky, a Washington, D.C.-area freelance writer, specializes in legal issues.