Stem cells are back in the spotlight after a Washington, D.C. district court issued a preliminary injunction halting the use of federal funding for research done using human embryonic stem cells.
|A colony of embryonic stem cells, from the H9 cell line (NIH code: WA09).
After simmering for nearly a decade on the backburner of public awareness, stem cells moved back to the forefront Aug. 23, when Judge Royce C. Lamberth of the District of Columbia District Court issued a preliminary injunction halting the use of federal funding for research done using human embryonic stem cells. In his ruling on the case of Sherley v. Sebelius, Lamberth found that using funds from the National Institutes of Health for human embryonic stem cell research violates a federal law, which states that federal funding of work resulting in the destruction of a human embryo is prohibited. Along with reigniting the ethical controversy over human embryonic stem cells, this court case promises to have far-reaching effects on the entire field of stem cell research.
A History of Stem Cells
Stem Cell Update
After a series of motions and hearings, on Sept. 28 the District of Columbia Court of Appeals permanently stayed the original preliminary injunction that barred use of federal funds for human embryonic stem cell research. This ruling means that National Institutes of Health review and funding of both new and renewing hESC grants can continue, as can intramural hESC research on the NIH campus.
Back at the district court level, both sides have submitted motions asking for summary judgment, which would allow Judge Lamberth to rule on the case in the absence of any further hearings. No date has been given for the ruling on summary judgment, though a decision is expected by the end of October. If these motions are denied, then a trial would be forthcoming.
For more up-to-date information, check out the ASBMB Policy Blotter.
Stem cells have traveled a long path to the present. The idea that a cell capable of regenerating damaged tissue existed in the body originated during the 19th century. However, the first true stem cells, by definition able to both self-replicate and differentiate into other cell types, were not isolated until hematopoetic stem cells were derived from bone marrow during the 1950s. Later work identified so-called adult stem cells in various other tissue types, including neural and intestinal tissues. Though used successfully to treat ailments such as leukemia, adult stem cells generally are constrained to forming a limited subset of cell types, exist at an exceedingly low frequency and are difficult to isolate. Researchers realized that an ideal treatment would instead use a highly pure, highly plastic, easily obtainable cell source.
The search for cells that could meet these high standards began in earnest in the 1970s, when researchers turned their attention to mouse tumors known as teratocarcinomas, in which random collections of cell types, such as teeth and hair, grow. The presence of such a diverse group of cells in one location led to the idea that the tumors contained highly plastic progenitor cells that were capable of differentiating into all somatic cell types. However, initial attempts to isolate these progenitors, termed embryonic carcinoma cells, directly from teratocarcinomas were plagued by inefficient yields and variable developmental potentials.
After years of trying, the holy grail finally was obtained when embryonic stem cells were isolated directly from early stage mouse embryos in 1981. Compared with heterogeneous embryonic carcinoma cells, these cultures contained homogeneous populations of pluripotent cells able to form unique cell types from each of the primary germ layers (endoderm, mesoderm and ectoderm). Subsequent work led to the development of protocols for efficient transformation of embryonic stem cells into a plethora of somatic cell types, including pancreatic, neural and even hematopoetic cells.
Embryos and the Question of Life
It took another 17 years before human embryonic stem cells could be successfully cultured in lab. Relying on excess, nonviable embryos donated from in vitro fertilization clinics, researchers ultimately were able to generate pluripotent human cell lines from which all adult tissue types could be obtained. To date, human embryonic stem cells successfully have been differentiated into numerous cell types, including pancreatic and cardiac cells, and, in 2009, the first clinical trial was approved by the U.S. Food and Drug Administration for use in treating spinal cord injuries.
Ethical issues immediately arose after the derivation of human embryonic stem cells, as groups questioned the morality of destroying human embryos for research purposes, leading to an extended legislative tug-of-war. The Dickey-Wicker amendment, which was added as a rider to the 1996 federal appropriations bill, prohibits “research in which a human embryo or embryos are destroyed,” thus apparently scuttling embryonic stem cell research. However, in 1999, Health and Human Services general counsel Harriet S. Rabb determined that federal funds could, in fact, be used for research on human embryonic stem cells, as this work did not involve the actual destruction of an embryo. Yet, no defined guidelines for funding human embryonic stem cell research existed until Aug. 9, 2001, when President Bush issued an executive order permitting the use of federal funds for research on established human embryonic stem cell lines but prohibited federal funds from being used to study any lines created subsequent to his announcement. Though initially encompassing 78 lines, researchers soon discovered that only 21 were viable for research and, that, having been derived before conditions had been optimized, even these lines were not ideal for use.
|President Barack Obama offers remarks before signing an executive order on stem cells and a presidential memorandum on scientific integrity in March 2009.
Hoping to further scientific and biomedical progress, Congress repeatedly attempted to expand on Bush’s decree, even passing two separate bills that would have allowed use of federal funds for stem cell lines derived after Aug. 9, 2001. But, each time, Bush vetoed the bills, claiming that, by allowing further destruction of human embryos, they would cross “a moral boundary” that “society needs to respect.” In March 2009, President Obama issued his own executive order that allowed for federal funds to be used for research on additional stem lines, that had been derived and propagated since 2001 using private funding. Obama’s ruling expanded the number of human embryonic stem cell lines approved for use by the NIH Human Embryonic Stem Cell Registry to 75, with more than 150 lines in line for review. However, neither Congress nor the administration altered the language set forth by the Dickey-Wicker amendment.
Loopholes and Legalese
The lack of congressional action to alter the Dickey-Wicker amendment was exploited by pro-life advocates James Sherley of the Boston Biomedical Research Institute and Theresa Deisher of AVM Biotechnologies, who, along with several religious groups, filed suit against the federal government, claiming that funds distributed by the NIH were being appropriated illegally for use on human embryonic stem cells, as they were derived via destruction of human embryos. The plaintiffs also claimed that, as adult stem cell researchers, they were at a competitive disadvantage when applying for NIH funds, as federal funding for human embryonic stem cell research “increase[d] competition for NIH’s limited resources.”
The district court originally rejected the lawsuit, finding that the plaintiffs lacked standing and had not suffered from “irreparable injury.” Upon appeal, the District of Columbia Court of Appeals found that the two researchers did, in fact, have standing and overturned the earlier decision. Forced to now consider the case on its merits, Lamberth found in favor of the plaintiffs, agreeing that their injury was “of such imminence that there is a ‘clear and present’ need for equitable relief to prevent irreparable harm” and that the injury was “beyond remediation.” His ruling rested on an unambiguous interpretation of the Dickey-Wicker amendment as prohibiting “all ‘research in which’ an embryo is destroyed.” By contrast, the federal government has maintained that federal funding of human embryonic stem cell research does not violate the Dickey-Wicker amendment, as federal funds are still prevented from being used for the actual derivation of human embryonic stem cells and that the statute is ambiguous in its definition of the term “research.”
As the fate of stem cell research plays out in the courtroom, it seems that patients and researchers can only sit and hope for a positive outcome. However, their focus need not be limited to lawyers and judges: Congressional leaders have indicated their willingness to enact legislation that will continue to support stem cell research. Moreover, scientists recently have developed alternative techniques to deriving human embryonic stem cells that do not rely on the destruction of human embryos, using both induced pluripotent stem cells and preimplantation genetic diagnosis-based technology.
The seemingly unlimited potential of human embryonic stem cells provides researchers with heretofore unknown hope for cures to diseases such as diabetes, Parkinson’s and Alzheimer’s. Everyone can agree that helping those suffering from these ailments should not be constricted by politics. In that light, as public support continues to grow, it seems that human embryonic stem cell research will soon be the rule rather than the exception.
Geoffrey Hunt (email@example.com) is an ASBMB science policy fellow.