Programs: Science and Policy
AAAS Policy Brief: Stem Cell Research
- Scientific Breakthrough
- Ban on Embryo Research
- Ethical Dispute
- NIH Guidelines
- Anticipation Builds
- The President's Decision
- The Controversy over Cell Lines
- Pressure Builds in Election Year
- 2006: The First Veto
- Stem Cells in the States
- 2007: The Second Veto
- 2009: Another President's Decision
- The New NIH Guidelines
- The Injunction
The issue of stem cell research burst on the scientific scene in November of 1998 when researchers first reported the isolation of human embryonic stem cells (hESCs). The discovery, made by Dr. James A. Thomson, a biologist at the University of Wisconsin, Madison, offered great promise for new ways of treating disease. The cells, which are derived from several-day-old embryos, can theoretically differentiate into virtually any type of human cell, from blood cells to skin cells. Scientists hope to find ways of using them to repair damaged tissue. For a clear and concise description of stem cells and their potential, see the National Institutes of Health (NIH) report Stem Cells: Scientific Progress and Future Research Directions, executive summary.
Dr. Thomson's breakthrough work was not eligible for funding from NIH, the federal government's primary sponsor of biomedical research and the sponsor of some of his other research projects. Instead, he set up a separate lab to work on hESCs supported by private funding from the Geron Corporation of Menlo Park, California and the Wisconsin Alumni Research Foundation (WARF).
The work was ineligible for public funding because of a ban placed by Congress on NIH-funded human embryo research. In 1995, Congress attached the ban to the bill appropriating funds for NIH. It has been retained in each successive appropriations bill (appropriations bills are passed annually), and until 2001, no public funding was ever provided for hESC research in the United States. The following is the text of the ban, originally authored in 1995 by then-Rep. Jay Dickey (R-AR) and then-Rep. Roger Wicker (R-MS), as it appeared in NIH's fiscal year 1996 appropriations bill (H.R. 3010, Sec. 128):
—None of the funds made available in this Act may be used for—
(1) the creation of a human embryo or embryos for research purposes; or—For purposes of this section, the phrase 'human embryo or embryos' shall include any organism, not protected as a human subject under 45 CFR 46 as of the date of the enactment of this Act, that is derived by fertilization, parthenogenesis, cloning, or any other means from one or more human gametes.
(2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero under 45 CFR 46.2048(a)(2) and 42 U.S.C. 289g(b).
Because of the great potential promised by Dr. Thomson's discovery, NIH sought legal counsel from the Department of Health and Human Services (HHS) on the application of the ban to hESC research. In January 1999, HHS concluded that scientists could use public funds for research on hESCs as long as derivation of the cells—which results in the destruction of an embryo—was carried out with private funds. NIH thus began drafting guidelines governing funding for hESC studies.
Opponents of hESC research hold that human life begins as soon as an egg is fertilized, and they consider a human embryo to be a human being. They therefore consider any research that necessitates the destruction of a human embryo to be morally abhorrent.
Proponents of hESC research, meanwhile, point out that in the natural reproductive process, human eggs are often fertilized but fail to implant in the uterus. A fertilized egg, they argue, while it may have the potential for human life, cannot be considered equivalent to a human being until it has at least been successfully implanted in a woman's uterus.
In vitro fertilization clinics routinely create more human embryos than are needed over the course of a fertility treatment, and are therefore left with excess embryos that are often simply discarded. Proponents of research hold that it is morally permissible to use such embryos for potentially life-saving biomedical research. Opponents object to this argument, however, saying that such research would still condone the destruction of embryos.
Some opponents of hESC research also argue that research on stem cells obtained from adults is just as promising and renders hESC research unnecessary. Most scientists, however, dispute this claim, citing great potential in the field of adult stem cells but several drawbacks as compared with hESCs. Proponents of hESC research advocate funding for both fields.
In December of 1999, NIH released draft guidelines allowing federally funded research on hESCs derived in the private sector and providing for stringent oversight of such research. The guidelines allowed research on cells derived only from embryos leftover from fertility treatments and donated with the consent of the progenitors. In addition, if a fertility clinic were to profit from the sale of embryos used for stem cell derivation, research on those cells would not be allowed. After reviewing a flood of comments, NIH released final guidelines on August 25, 2000, and with the backing of President Clinton, solicited applications for its first hESC research grants.
The guidelines were greeted with mixed reviews: praise from many supporters of hESC research and criticism from opponents. NIH received several grant applications for work on hESCs under the new guidelines, and it established a committee to review the proposals. However, a statement by soon-to-be President Bush during his 2000 campaign indicated his opposition to hESC research and discouraged many scientists from submitting proposals.
Bush said, "I oppose federal funding for stem cell research that involves destroying living human embryos." Because of this statement, some speculated that he would overturn the NIH guidelines as one of his first acts as president. The president stood by his statement, but he resisted calls to overturn the guidelines outright and instead ordered a review by Secretary of Health and Human Services Tommy Thompson. In April, NIH canceled the first scheduled meeting of its committee set up to review grant applications for stem cell research. In a letter to the Culture of Life Foundation dated May 18, 2001, President Bush reiterated his campaign statement.
During the president's first few months in office, he delayed his decision on the guidelines and repeatedly rebuffed attempts by reporters to get him to talk about the issue. Meanwhile, media attention on stem cell research built gradually until the topic reached the front pages in early summer of 2001. On July 9, stem cells graced the cover of Newsweek magazine. Reports surfaced of a divided White House as President Bush sought a compromise.
Interest groups on each side of the issue waged intense lobbying campaigns. Patient groups, scientific organizations, and the biotechnology industry lobbied President Bush to go forward with federal funding for hESC research, while conservative anti-abortion groups and the Catholic Church urged him not to do so.
In Congress, most Democrats and moderate Republicans argued for hESC research, while most conservatives oppose it. However, there were and continue to be a few staunch conservatives who support stem cell research, such as the late Sen. Strom Thurmond (R-SC) and former Sen. Connie Mack (R-FL). On June 13, 2001, Sen. Orrin Hatch (R-UT), who led the fight in the early 1990s against fetal tissue research, came out strongly in favor of stem cell research. He set out his views in a 10-page letter to Secretary Thompson. At a hearing the following month, Sen. Bill Frist (R-TN), a surgeon who has often advised President Bush on health-related issues, announced his support for hESC research that is confined to "a limited number of cell lines."
President Bush announced his decision in a primetime address to the nation on August 9, 2001. He decided to allow federal funding of hESC research to go forward, but only on cells already in existence. After researchers isolate stem cells from a human embryo, the cells often replicate indefinitely, creating a "cell line." The president decided that for a cell line already in existence, research would be permissible because destruction of an embryo had already taken place, but he refused to allow publicly funded research on any cell line created in the future so as to prevent the federal government from acting in a way that would encourage the destruction of human embryos.
This decision drew mixed reactions from groups on each side of the issue. Some opponents of hESC research praised the decision for limiting research to existing cell lines, while others said that no research should be permitted under any circumstances. Proponents of hESC research, meanwhile, generally praised the president for allowing some research to go forward, but criticized the restriction to existing cell lines as too strict, questioning whether enough research would be allowed.
Key to President Bush's decision was a determination by NIH that there were 64 cell lines in existence worldwide as of August 9. Previously, most scientists had thought the number to be much lower, and some expressed doubts about how many of the 64 cell lines would be truly useful to researchers and meet the stringent ethical requirements set out in the NIH guidelines and imposed by many universities. On August 27, NIH released a statement listing the ten entities that had created the cell lines and announcing plans to create the Human Embryonic Stem Cell Registry, which would contain more detailed information about the hESC lines eligible for federally funded research. The agency also encouraged researchers to submit grant applications for hESC research and requests to use existing funds for such research.
The president also announced during his speech the formation of a President's Council on Bioethics, chaired by Dr. Leon Kass, a bioethicist at the University of Chicago. In addition to studying a range of ethical issues raised in the biomedical and behavioral sciences, the council oversees all federally funded hESC research.
According to the August 27, 2001, NIH statement, there were 64 cell lines in existence as of August 9 at the following ten laboratories:
|Name||Number of cell lines|
|BresaGen, Inc., Athens, Georgia||4|
|CyThera, Inc., San Diego, California||9|
|Karolinska Institute, Stockholm, Sweden||5|
|Monash University, Melbourne, Australia||6|
|National Center for Biological Sciences, Bangalore, India||3|
|Reliance Life Sciences, Mumbai, India||7|
|Technion-Israel Institute of Technology, Haifa, Israel||4|
|University of California, San Francisco, California||2|
|Göteborg University, Göteborg, Sweden||19|
|Wisconsin Alumni Research Foundation, Madison, Wisconsin||5|
Scientists raised concerns about these cells centering on five questions: whether the cell lines were indeed robust stem cell colonies; whether the procedures used to create the cells were consistent with high ethical standards; whether the different cell lines had sufficient genetic diversity; whether cells produced from the cell lines would be safe for implantation in humans; and whether the owners of the cell lines would make them available to researchers in a timely fashion and at a reasonable cost.
NIH claimed that 19 stem cell lines existed at Göteborg University in Sweden . However, The New York Times reported that of these 19 lines, 12 were "still in early stages," four were "being studied and described," and just three were "established." Referring to the cells in early stages, Professor Lars Hamberger, a scientist at the Göteborg lab, told the Times that "[t]hose 12 perhaps ought to be called potential cell lines. If we get three good lines out of them we’ll be satisfied."
In an appearance before the Senate’s Health, Education, Labor and Pensions (HELP) Committee on September 5, 2001, Secretary Thompson acknowledged that just 24-25 of the cell lines were in fact established embryonic stem cell lines. He emphasized, however, that there were 64 "derivations" and that while some were in early stages of development, all were derived before August 9 from surplus embryos created by fertility clinics, making them eligible for use by federally funded researchers.
Regarding ethical requirements, the NIH statement said that all of the 64 cell lines "meet the President’s criteria." In other words, they "must have been derived from an embryo that was created for reproductive purposes and was no longer needed," and "informed consent must have been obtained for the donation of the embryo and that donation must not have involved financial inducements." The statement did not indicate, however, whether the cells would be likely to meet the strict ethical standards enforced by many universities.
Also in doubt was the genetic diversity of the cells. In order to account for genetic differences in studying stem cells, researchers need to carry out experiments on cells derived from a group of embryos that is genetically variable. While NIH revealed the locations of the existing cell lines, their origins remained uncertain.
The safety of the existing cell lines for implantation also emerged as a major concern. Most of the cells grew in culture with the help of mouse stem cells, which could potentially introduce animal viruses dangerous to humans. Under Food and Drug Administration rules, such transplants with existing cells would be classified as "xenotransplants," or transplants of animal tissue, and would be subject to strict requirements on both researchers and patients.
In order to address concerns about the access researchers would have to existing cell lines, Secretary Thompson announced at the HELP Committee hearing that NIH had signed a memorandum of understanding with WiCell Research Institute, which is affiliated with WARF. The agreement provided NIH scientists with access to WiCell's stem cell lines for their research and allowed them to freely publish their results.
On November 7, 2001, NIH launched the Human Embryonic Stem Cell Registry. The registry listed all the cell lines eligible for federally funded research, along with contact information for researchers wishing to utilize them. For some of the cell lines, additional characterization information was also posted. Along with the creation of the registry, NIH issued notices formally inviting grant applications for research on the approved cell lines, withdrawing the Clinton Administration guidelines and explicitly delineating President Bush's criteria for embryonic stem cell research.
The following year, the National Academy of Sciences released a report on stem cells that concluded that public funding should be made available for research on both embryonic and adult cells, and that in the long run, it would be necessary to derive new embryonic stem cell lines.
As of August 14, 2002, a year after President Bush announced his stem cell policy, the NIH stem cell registry listed 78 eligible cell lines that met the president's criteria for publicly funded research. NIH reached agreements with four organizations to allow its researchers to use those organizations' cell lines. The agency also awarded several infrastructure awards to facilitate the distribution of the cells.
However, many of the questions raised by scientists about the stem cell policy remained unanswered. News reports indicated that only about 16 of the 78 eligible cell lines were available for distribution, and only a handful had made it into the hands of researchers. Some scientists expressed concern that the slow pace of research in the United States would allow other countries to assume a leadership role in the field.
The stem cell debate reappeared in full force in 2004. By that point, it was widely reported that the original number of embryonic stem cell lines deemed available for federal research in August 2001 had been overestimated and many of those cell lines were perhaps unsuitable for research. Many prominent scientists and varying health organizations spoke out in favor of reforming the President’s policy. In particular, the public pleas for increased support of embryonic stem cell research by the family of former President Reagan helped push stem cells into the daily headlines.
In April, a bipartisan collection of 206 Representatives sent a letter to President Bush requesting a loosening of the limits on federal embryonic stem cell research. The President received a similar letter in early June from 58 Senators, including Orrin Hatch (R-UT) and Kay Bailey Hutchison (R-TX).
Reps. Mike Castle (R-DE) and Diana DeGette (D-CO) sponsored, along with the support of 189 bipartisan House members, H.R. 4682, the Stem Cell Research Enhancement Act of 2004. While not specifying funding, this legislation called for increasing federal support of embryonic stem cell research. It would have allowed the use of stem cells derived from embryos that had been donated from in vitro fertilization clinics and that would have otherwise been discarded. The bill came to rest in the Subcommittee on Health of the House Energy and Commerce Committee.
During the 2004 election, embryonic stem cell research became a defining issue between the two major presidential candidates. Sen. John Kerry (D-MA), the Democratic nominee, firmly called for increased federal funding of stem cell research and a repeal of the restrictions set in the August 2001 policy. Stem cell research even received prime-time billing in the Democratic National Convention with a speech by Ron Reagan Jr. The Bush Administration stood firmly by its policy and even First Lady Laura Bush, not known for her involvement in policy issues, came out in defense of the research limitations in a campaign rally.
In mid July 2004, NIH announced plans to develop a National Stem Cell Bank that would consolidate some of the available embryonic cell lines into one location. Many opponents of the present restrictions saw the Cell Bank as a superficial arrangement to stifle the growing public dissonance and mask the serious problems with the existing embryonic cell lines.
HHS issued a press release that same month highlighting President Bush's position on embryonic stem cells. It reiterated the Administration's stance that taxpayer dollars should not fund the destruction of human embryos, regardless of the source.
In February 2005, Castle and DeGette again introduced the Stem Cell Research Enhancement Act, H.R. 810. This time the bill gained enough steam to pass the House three months later with a bipartisan vote of 238-194. In the Senate, hESC research proponents such as Sen. Arlen Specter (R-PA), head of the Appropriations panel responsible for NIH funding, called for consideration of the bill. Majority Leader Bill Frist (R-TN) gave scientists hope when he announced in July 2005 that he had decided that the President’s policy was too restrictive and that he would support H.R. 810.
After a yearlong delay in which the Senate leadership grappled with how best to bring the issue to the floor, Frist announced a plan in June 2006: The Senate would consider three bills, with no amendments, that would each require 60 votes to pass. One of them was H.R. 810. Supporters of H.R. 810 were pleased with the agreement; some had feared that, were the Senate given opportunity to amend H.R. 810, the bill would be slowed or killed as it was forced to go through the conference committee process.
The other two bills up for consideration were S. 2754, a bill to encourage research into methods of obtaining cells similar to hESCs that would not destroy human embryos, and S. 3504, a bill that would prohibit the establishment of “fetal farms,” in which embryos would be harvested solely for research purposes. Specter teamed with his conservative counterpart in Pennsylvania, Republican Rick Santorum, to sponsor S. 2754. Santorum also sponsored S. 3504 along with fellow hESC research opponent Sam Brownback (R-KS).
On July 18, the Senate passed all three bills. H.R. 810 passed with a vote of 63-37; the other two received unanimous votes of acceptance. To be veto-proof, the bill would have had to pass with 67 votes.
But some surprises were in store in the House, where the two Senate bills were placed on the suspension calendar—a speedy vote process that eliminates floor amendments and enables bills to pass quickly with a supermajority, two-thirds of the vote. Pundits expected both bills to pass easily. Instead, only S. 3504 survived. Some Democrats indicated that S. 2754 would provide a form of political cover to the President to reject H.R. 810, and so the bill lost. The Republican leadership could have then attempted to bring up the bill again under normal procedures. Though S. 2754 had the votes to pass with a simple majority, a floor debate would have given Democrats a chance to steal the media spotlight from the President.
So two bills went to the President for his signature, and as expected, the President made S. 3504 law and vetoed H.R. 810. It was the first veto of his five-plus-year presidency. Bush justified the veto by saying the bill “crosses a moral boundary that our decent society needs to respect.”
The House failed to muster up the necessary votes to override the veto; thus, the stem cell landscape for now remains at status quo.
As hESC scientists had reason to fret over the lack of available funds, some states took steps to help fill in some of the gaps. In 2004, New Jersey became the first state to appropriate funding for hESC research. Later that year, California voters approved Proposition 71, which allocated $3 billion over 10 years to stem cell research. Connecticut, Illinois, Maryland, and New York followed with funding initiatives of their own.
In January 2007, after a crop of freshman lawmakers took office, the House again passed the Stem Cell Research Enhancement Act (H.R. 3) with a vote of 253-174. The Senate followed suit in April (S. 5) with a vote of 63-34, which indicated that the Senate was likely one vote shy of a veto override. (Three Democratic senators who favored the bill in the past did not vote; their votes would bring the tally to 66 supporters.) Unlike H.R. 3, S. 5 contains additional provisions encouraging research into alternative methods of deriving stem cells. This is largely symbolic, as these alternative methods are already eligible for NIH funding. The Senate passed another bill, S. 30 , which calls solely for the funding of alternative methods; the vote was 70-28. S. 5 made it through the House on June 7 with a vote of 247-176. (The alteration from the previous vote on H.R. 3 had to do with a change in the makeup of nonvoting members.) On June 20 the President vetoed S. 5 and issued an executive order similar to the stalled S. 30-it encourages research into alternative methods of deriving stem cells.
Opponents of President Bush's stem cell policy were buoyed by the election of Democratic Sen. Barack Obama as the 44th U.S. President. Obama had pledged to overturn the Bush policy and thus expand the number of human embryonic stem cell lines eligible for federally-funded research. On March 9, he did so through an executive order. The order did not lay out specific ethical guidelines but rather allowed 120 days for the development of such guidelines by the secretary of Health and Human Services through the director of the National Institutes of Health.
Stem cell champions in Congress still sought to codify the new stem cell policy through another Stem Cell Research Enhancement Act. DeGette and Castle reintroduced that bill (H.R. 873) in the House, as well as a bill called the Stem Cell Research Improvement Act (H.R. 872), which contained additional guidance and reporting requirements for NIH. Senators Harkin and Specter also reintroduced their bill (S. 487), the same one Bush vetoed in 2007.draft guidelines allowing funding for research on stem cells derived from donated embryos leftover from fertility treatments, provided that certain conditions be met, such as the voluntary informed consent of donors. NIH would continue to fund research on adult stem cells and induced pluripotent stem cells, which are adult cells that have been directed by scientists to take on properties of embryonic stem cells. However, it would not fund research on embryos created specifically for research or on stem cells derived by research cloning techniques or by parthenogenesis (a method that uses unfertilized egg cells). Acting Director Raynard Kington justified the approach by stating that the method approved by NIH had broad public support.
During the month-long public comment period, the guidelines received more than 49,000 comments. Scientific groups were largely pleased with the speed of NIH's announcement, but they were mixed on the content. Many applauded the guidelines, including AAAS, which said they represented "important progress." But other stem cell advocates were disappointed that they did not allow funding for enough types of research. (Obama's executive order mandated that NIH periodically revisit the guidelines.)
The guidelines required strict informed consent provisions that appeared to be modeled largely on the NIH guidelines from 2000 and guidelines devised by the National Academies in 2005. Donors would not be allowed to receive money or other incentives for their embryos, and the decision to donate must be free of influence of researchers and separate from the decision to seek fertility treatments. Researchers and their institutions must provide documentation for several requirements, including that the donor was aware of all options for use of the embryos, that the donor understood what would occur to the embryos in research, and that the donor was not able to direct use of the stem cells to any particular individual's medical care.
Though most research supporters recognize the importance of informed consent rules, the fact that the specific requirements for the documentation of informed consent have changed over the years made many nervous about the eligibility of stem cell lines employed in ongoing studies, including the lines that were eligible for Bush-era funds.
In response to these concerns, NIH officials decided in the final guidelines, which took effect July 7, 2009, that previously-derived stem cell lines that follow the spirit of the new ethical guidelines - if not the exact documentation requirements - would be eligible for funding. According to the final guidelines, an NIH advisory panel would evaluate these older stem cell lines if needed, and the ultimate determination on whether they would qualify would rest with the NIH director.
The following week, NIH posted a notice about how it would handle applications and awards for human embryonic stem cell research. It provided guidance for ongoing research projects and gave a status update on pending applications.
The Dickey-Wicker Amendment currently continues to be a part of congressional appropriations bills and thus no federal funds can go toward research that creates or destroys a human embryo. So far several pressing legislative priorities have taken precedence over stem cell legislation in the 111th Congress.
On August 23, 2010, U.S. District Judge Royce C. Lamberth issued a preliminary injunction barring NIH from funding human embryonic stem cell research.
The injunction was in response to a lawsuit involving two scientists, James L. Sherley of the Boston Biomedical Research Institute and Theresa Deisher of AVM Biotechnology in Seattle, who argued that the funding of embryonic stem cell research would cause them "irreparable injury" by increasing competition and therefore potentially taking funds away from adult stem cell research, their area of work. Judge Lamberth agreed. The judge also ruled that federally funded embryonic stem cell research was illegal under the Dickey-Wicker Amendment and that it is not possible to disentangle embryonic stem cell research from the derivation of the stem cells, even if the cells are derived using private funds.
When the case first came before Judge Lamberth in 2009 he rejected it, saying the plaintiffs did not have standing to file suit. At that time the plaintiffs included not just the two scientists but also the Christian Medical Association, Nightlight Christian Adoptions, two couples seeking to adopt embryos, and "embryos" themselves. A U.S. Appeals Court subsequently ruled that Sherley and Deisher, but not the other plaintiffs, did have standing to file suit and sent the case back to Lamberth for consideration.
The U.S. Justice Department quickly moved to appeal the injunction. Meanwhile, NIH was forced to shut down its intramural human embryonic stem cell experiments and halt any grants or renewals that had not yet been paid out. Research that was already in progress was allowed to continue until at least the next renewal period. Embryonic stem cell scientists faced a sudden and significant disruption to their work.
Stem cell research champions in Congress quickly mobilized to ponder legislative strategies for doing away with the injunction, perhaps by overturning or clarifying the language of the Dickey-Wicker Amendment, but acknowledged the need to factor in the midterm elections just two months away.
On September 9, the U.S. Appeals Court for the D.C. Circuit granted the government's request to stay the injunction temporarily until the court could hear oral arguments regarding the injunction. During the roughly two-week period, NIH was able to fast-track some of the grants that had previously been on hold. A three-judge panel heard oral arguments on September 27 and on the following day ruled that federal funding of hESC research could continue while the appeals process moved forward.
For FY 2011, NIH has estimated $358 million of its budget would go toward human non-embryonic stem cell research and $126 million would go toward human embryonic stem cell research.
On July 27, Lamberth ruled on the underlying case, and to the surprise of many observers decided in favor of the Obama policy, dismissing the lawsuit. He felt compelled to follow the reasoning of the Appeals Court—though he didn't seem happy about it, saying “this court has become a grudging partner in a bout of 'linguistic jujitsu,'” referring to the dissenting opinion of one of the Appeals Court judges.
Updated August 12, 2011