November Biotechnology Ballot Measures: GMO Labeling, Fetal Personhood, GMO Cultivation

The 2014 midterm elections contained a number of state ballot measures on policy issues involving biotechnology. Not surprisingly, the issue of whether foods containing genetically engineered ingredients should be labeled appeared on two state ballots. In Oregon, Measure 92 was apparently narrowly defeated (50% to 49%) (Oregon had also rejected a similar ballot measure in 2002). However, the narrowness of the vote has now resulted in this week's order of a recount. With respect to Colorado's proposed labeling measure, the vote was not so close: Proposition 105 was defeated 65%-34%. These defeats mean that the current status of state labeling measures is that Vermont has fully passed a labeling law that takes effect in 2016; Connecticut and Maine have also passed labeling laws but their implementation is conditionally linked to a trigger where neighboring states passing similar measures (which has not yet occurred). A second issue with implications for biotechnology on the ballots this month was the issue of fetal personhood: two such initiatives on the ballots in North Dakota and Colorado would have declared personhood to begin at the moment of conception; these and similar measures have been crafted by anti-choice groups in order to elevate the constitutional status of the unborn and effectively criminalize abortion as a result. However, conception-triggered personhood also has implications for the field of human embryonic stem cell (hESC) research: the use of such cells requires their removal from an early-stage embryo, and under a fetal personhood statute, effectively becomes a criminal act against a legally-declared person. As a result, these initiatives have also threatened hESC research. The measures in North Dakota and Colorado were both rejected (by almost identical margins of 65% to 35%). To date, all fetal personhood ballot measures in the states have failed. A third issue on the November ballots was agricultural, relating to the presence of genetically engineered crops: several county-wide ballot measures that would ban the planting and cultivation of genetically engineered crops (on the ballots as "genetically modified organisms") were passed in Humboldt County, California and Maui County, Hawaii.  Lastly, a bond measure in Maine to authorize funding
"to discover genetic solutions for cancer and the diseases of aging" passed overwhelmingly. The 2014 elections continued the ongoing attention to GMO labeling and fetal personhood initiatives as the most contentious state-based legislative  battles affecting biotechnology.

New Stem Cell Research Revives Legal Debates Over Human Cloning

Stem cell scientists report the successful use of somatic cell nuclear transfer (SCNT) to create human embryonic stem cells (hESC) from an adult donor, effectively creating a population of therapeutically available cells to treat disease. This general technique, called therapeutic cloning, affords an opportunity to treat patients with genetically identical stem cells for any number conditions where new cells or replacement cells are needed (e.g., diabetes, Parkinson’s, spinal cord injuries). The investigators were able to generate of embryonic stem cells from a 35-year old and a 75-year old donors. Earlier research had demonstrated the generation of hESC if fetal or infant cells were the donors. Because human embryos were created and used to derive the hESC, the new research revives debates over the potential for advances in therapeutic stem cell research to simultaneously open the door to the misuse of these techniques for reproductive cloning, the generation of a cloned embryo that could be implanted and brought to term (a dual-use characterization). 

This debate is not new – these questions emerged at the first publication and use of somatic cell nuclear transfer (SCNT) to create the cloned sheep, Dolly, in 1997. In that period, with the recognition that advancing technical achievements might result in attempts to try human reproductive cloning, legislative efforts to ban both therapeutic and reproductive cloning or only reproductive cloning emerged at the state and national level in the U.S., as well as internationally. Subsequent research since 1997 revealed that cloning (using somatic cell nuclear transfer, SCNT) was easier to achieve with animals than with humans, until now, which is why this new research puts human cloning back into debate. The flash points in the legal debate are several: whether embryos can be  created for the sole purpose of producing genetically optimal stem cells, whether embryos can be destroyed during the derivation of human embryonic stem cells – and then the dual-use dilemma where the creation of an embryo could be a predicate to stem cell derivation or to reproduction. The Bush administration imposed a ban on federal funding for the derivation of hESC, and only allowed funds to be used on existing cell lines. In 2009, the Obama administration reversed that course and issued guidelines which allowed federal funds to be used to derive new embryonic stem cell lines from already-existing embryos (from fertility clinics). NIH maintains a hESC registry that catalogues cell lines that can be studied with federal funds. In 2011, a legal challenge to the Obama policy emerged from several adult stem cell researchers who alleged that allowing federal funds for hESC research violated the federal Dickey-Wicker amendment, which prohibits the creation of embryos for research or the destruction of embryos during research (see earlier post). In Sherley v. Sebelius (D.C. Cir. 2012), the D.C. Circuit upheld the Obama policy, finding that destruction of embryos that occurs in the ESC derivation process was not a part of individual ESC research projects using already derived ESCs:

Therefore, ESC research is no more “research in which...embryos are...subjected to risk” than it was “research in which...embryos are...destroyed.”  

With the demonstration that hESC can be derived from older human donors, human therapeutic cloning appears more viable and commercially attractive (older patients with degenerative conditions are a prime target). Will this lead to a demand for new cloning-related laws to avoid the dual-use potential? It’s unlikely right now, as the new research is an expansion of already existing technologies, rather than a paradigm-shifting breakthrough. Yet, making human embryo cloning technically possible revives the concerns that animated late-1990s legislative activity. For example, recently introduced legislation, H.R. 2433, distinguishes federal support for embryonic stem cell research from any endorsement of "human cloning:"

Defines "human cloning" to mean the implantation of the product of transferring the nuclear material of a human somatic cell into an egg cell from which the nuclear material has been removed or rendered inert into a uterus or the functional equivalent of a uterus. 

Yet, another bill, H.R. 2164, would prohibit both therapeutic and reproductive cloning with its more expansive definition of human cloning:

(1) Human cloning.--The term `human cloning' means human asexual reproduction, accomplished by introducing the nuclear  material of a human somatic cell into a fertilized or unfertilized oocyte whose nucleus has been removed or inactivated to produce a living organism (at any stage of development) with a human or predominantly human genetic constitution. 

A patchwork of state laws address cloning: several states maintain bans on all human cloning (prohibit conduct per se, or disallow use of state funds), while other states allow therapeutic, but not reproductive cloning (including authorizing use of state funds). The stem cell field is more scientifically complex now than it was in 1998, with techniques using adult stem cells and induced pluripotent stem cells (neither of which are derived from human embryos) also competing for therapeutic supremacy, and avoiding the legal and moral questions attaching to the derivation and use of hESC.

D.C. Circuit Upholds FDA Regulation of Autologous Stem Cell Therapies

The FDA continues to monitor the emerging field of stem cell medicine, which offers the possibility of treating certain medical disorders by the application of new cells which replenish deteriorating tissues (e.g., Parkinson’s, heart disease, diabetes). The prospect of harvesting a patient’s own stem cells and administering them to sites of cellular stress is a new paradigm for disease treatment (autologous stem cell therapy). Nonetheless, such practices challenge existing legal regimes which regulate the introduction of pharmaceutical and biologic products into the marketplace. Regenerative Sciences, Inc., is a Colorado corporation that its Regenexx stem cell treatment, offered to patients suffering from a number of musculoskeletal conditions. The procedure involves withdrawing bone marrow from a patient, extracting the mesenchymal stem cells from the marrow, and processing the cells to create a therapeutic preparation for injection to a site of interest, with a goal of restoring function to impaired joints. Since 2008, the FDA has cautioned the company that its practice was likely violating the Federal Food Drug and Cosmetic Act (FDCA) because it involved the use of an unapproved drug and likely violating the a biological product under the Public Health Service Act (PHSA), because it used an unapproved biologic product. The FDA also inspected the Regenerative facilities in 2009, and found numerous departures from good manufacturing practices. The FDA then sued to enjoin the company from offering unapproved stem cell treatments and prevailed in federal district court in 2012. The court granted summary judgment on a motion by the FDA that the Regenerative stem cell preparation was both a drug and a biologic, and, as such, was both adulterated and misbranded, in violation of both statutes (see earlier post). The court issued a permanent injunction against Regenerative, prohibiting it from offering the stem cell treatment. 

Now, the D.C. Circuit has upheld the district court’s decision, rejecting the defendant’s arguments that it was simply engaged in the practice of medicine, which is not regulated by the FDA, and is governed by state law. The appellate court affirmed the lower court’s finding that the stem cell preparation was both a “drug” and a “biologic” and required FDA approval before use in clinical medicine, noting that these existing laws do not interfere with the practice of medicine:

Appellants’ construction of the FDCA, by contrast, would allow states to gut the FDCA’s regulation of doctors, and thereby create an enormous gap in the FDCA’s coverage, by classifying the distribution of drugs by doctors as the practice of medicine. Given Congress’s intent that the FDCA’s “coverage be as broad as its literal language indicates," United States v. An Article of Drug . . .Bacto-Unidisk, 394 U.S. 784, 798 (1969), such a construction is not tenable. 

Critics of these FDA enforcement activities argue that the application of the standard drug approval process to stem cell therapies (especially with the use of autologous cells harvested from the patient) undercuts innovation in the field. Proponents of FDA regulation argue that existing statutory responsibilities call for the agency to monitor the use of stem cell therapies, yet some concede that the use of autologous stem cell therapies calls for a novel regulatory policy that is especially tailored to these procedures, rather than the application of “one size fits all” FDCA and PHSA requirements.

Fetal Personhood Efforts Continue; North Dakota Ballot Measure in 2014

The fetal personhood movement has resurfaced in North Dakota, as the legislature has approved a 2014 ballot measure that will offer the following constitutional amendment: “The inalienable right to life of every human being at any stage of development must be recognized and defended.” This measure aims to establish legal personhood for the fertilized egg, embryo and fetus, with the attendant implications for the assertion of reproductive rights (a bill in the state to directly install fetal personhood by statute failed last week). North Dakota is the first state to approach fetal personhood by legislatively-referred constitutional amendment, in contrast to the citizen-originated beginnings for other state initiatives. Fetal personhood initiatives have been on the ballot before, twice in Colorado (defeated 2008 and 2010) and in Mississippi (defeated in 2011; see here). The Oklahoma Supreme Court invalidated a proposed personhood initiative in 2012 (in a pre-ballot constitutional review), ruling that the initiative was unconstitutional because it could not be reconciled with Planned Parenthood v. Casey (1992) (establishing the “undue burden” standard to assess the legality of measures restricting the exercise of the right to abortion). At the federal level, the Life at Conception Act has been introduced in the Senate and the Sanctity of Human Life Act in the House. The latter states: 

[T]he life of each human being begins with fertilization, cloning, or its functional equivalent, irrespective of sex, health, function or disability, defect, stage of biological development, or condition of dependency, at which time every human being shall have all the legal and constitutional attributes and privileges of personhood...  

While the fetal personhood movement has largely originated as an attempt to limit reproductive rights, most clearly abortion and certain forms of birth control, the impact of shifting legal personhood to the prenatal stage affects other life science technologies. In vitro fertilization is a commonly used assisted reproductive technology (ART) in which embryos are created in vitro (outside the body) for implantation and pregnancy. In the process, some embryos are either destroyed or unused, and legal personhood for the embryo could potentially upend how IVF is performed, if at all. Fetal personhood further impacts the use of embryonic stem cell techniques, in which stem cells are derived from embryos leftover from IVF procedures and are used to treat various kinds of cellular degeneration (e.g., Parkinson’s disease). Elevating the legal status of the embryo could potentially derail this field of research and medicine. Therefore, fetal personhood strikes at reproductive rights, fertility treatments and stem cell therapies. At the present time, renewed efforts are underway in Mississippi as well as other states to place personhood initiatives on the ballot. The decision from the Oklahoma court on that state’s failed initiative is instructive, because the fetal personhood efforts began in response to the invalidation of many abortion-restricting laws in the country under either Roe v. Wade (1973) or Casey. However, the Oklahoma court applied the same constitutional lens to the proposed amendment that it would apply to more routine abortion restrictions, suggesting that the legal strategy of fetal personhood may be more legally vulnerable than its proponents have hoped.

Supreme Court Will Not Review Funding of Stem Cell Research

The Supreme Court has turned down an opportunity to review the legal challenge to the Obama policy on federal funding of embryonic stem cell (ESC) research. In 2009, President Obama reversed the Bush-era ban on using federal funds to derive new ESC lines. In Sherley v. Sebelius, several federally funded adult stem cell researchers had challenged Obama’s policy as a violation of the Dickey Wicker amendment, which prohibits the use of federal funds for any research in which an embryo is destroyed. Earlier this year, the Court of Appeals for the D.C. Circuit upheld a lower court’s ruling that the Obama policy did not violated the legislative ban. The Supreme Court has now denied the challengers’ petition for certiorari. Researchers in the field can expect stability through the second Obama term. After that, a new executive policy in 2017 could again impair funding, but the field has advanced over these last four years. The fully funded ESC field has now generated many new ESC lines, which place the field in a stronger position than in was in 2009. The NIH Stem Cell Registry now lists about 200 available cell lines, in contrast to about 20 that were available during the Bush policy years. Nonetheless, the prospect of future volatility in funding policy remains an unwelcome distraction for the field. One only has to look at the impact that the sequestration debate in Washington (mandatory spending cuts to kick in March 1) has had on the biomedical research community as it adjusts to the fact that the NIH may be facing an 8.2% reduction in its budget if sequestration is not avoided by Congress.

Post-Election: No Labels, Stem Cell Research, Congressional Committees

The election results are in, with consequences for several high-profile biotechnology issues at stake. Voters rejected California's Proposition 37, which would have required the labeling of genetically engineered (GE) foods in the state (see here). A vigorous campaign occurred in the state, of which opponents outspent supporters by about 5 to 1. An effective source of opposition to the measure was based on arguments that this new law would have adverse economic consequences - for consumers (higher prices), businesses (compliance) and a cash-strapped state (administrative costs). The final vote was 53% opposed, 46% in favor; this would have been the first state to enact such a law. The movement to label GE foods continues, with upcoming efforts on deck in Washington and Oregon. In a separate issue, the reelection of President Obama cements his policy of allowing federal funds to be used for embryonic stem cell research (see here), so this biotechnology sector has stability for at least several years. At a meta-level, impacting the major life science agencies such as NIH and the FDA, neither house of Congress changed hands (keeping committee leaderships in place), so that leadership of key committees in the House, such as the Committee on Science, Space and Technology, remains a GOP preserve, while the Democrats retain control of the Senate and its Committee on Health, Education, Labor and Pensions (HELP). The Obama reelection also locks in the Affordable Care Act (see here). Lastly, Charles Darwin received 4,00 write-in votes in a Georgia congressional election where the incumbent Rep. Paul Broun (R), a member of the House Committee on Science, Space and Technology, is an outspoken opponent of the theories of evolution, embryology, and Big Bang cosmology. Broun was reelected.

Biotech on the Ballot: Labeling of Genetically Engineered Food and Funding of Stem Cell Research

A preview of the biotechnology-related election issues on the November 6 ballot illustrates both direct and indirect implications of the upcoming vote. Two areas of biotechnology and the law will be clearly impacted by the results of state and national elections - the partial regulation of genetically engineered food through labeling, and the federal funding of embryonic stem cell research. The most directly consequential measure (yes/no) is in California. There is a state ballot initiative to require the labeling of genetically engineered (GE) foods in California, Prop 37; if adopted, it would be the first such state mandate to be imposed (see here). Thus, on November 7th, California could be looking at implementing a regime of mandatory labeling for GE foods, and we could expect legal challenges to follow with likely First Amendment challenges to the labeling, where the contours of the commercial speech doctrine would be at issue (e.g., somewhat analogous to International Dairy Foods Association v. Amestoy (2nd. Cir. 1996), where the 2nd Circuit invalidated a Vermont measure requiring hormone-related labeling of dairy products). 

It is also foreseeable that the outcome of the Presidential election will indirectly (but seriously) affect the status of stem cell research in the U.S. – specifically the ongoing controversy over the federal funding of embryonic stem cell research (see here). In 2009, President Obama reversed the Bush-era policy of disallowing the use of federal funds for the derivation of new embryonic stem cell lines; as a result, the National Institutes of Health (NIH) is allowed to award grants for such research. The Romney website contains a policy on stem cell research; while not directly addressing the use of federal funds for embryonic stem cell research, the statement is written to focus on alternatives: “Adult stem cell research and alternative methods to derive pluripotent stem cells, such as altered nuclear transfer and direct reprogramming, are scientific paths that carry much promise and avoid raising ethical concerns.” Governor Romney vetoed a Massachusetts bill in 2005 that would have allowed “therapeutic cloning” – the creation of a cloned embryo to derive genetically compatible embryonic stem cells (this debate was extant in federal legislative battles at that time, with Democrats and Republicans having opposing positions). The 2012 campaign site contains this statement: “When confronted with the issue of stem cell research as governor of Massachusetts, Mitt Romney chose to support life by vetoing a bill that would have allowed the cloning of human embryos.”  Actually, this is a veto more grounded in a rejection of deliberate embryo creation rather than the stem cell research itself. Thus, this statement does not address whether Romney would allow the funding to derive embryonic stem cells from leftover or discarded embryos that were created not for research, but in the process of assisted reproductive technologies (e.g., at fertility clinics). However, from all available evidence, it can be inferred that the Romney position will be to undo the Obama policy of federal funding for new stem cell lines from unused embryos.  Thus, on November 7th, the stem cell community wil either encounter the status quo (Obama) or the possible elimination of federal funds for embryonic stem cell research (Romney); a Romney win would also obviate the current legal challenges to the Obama policy. On a final note, the larger specter of federal support for scientific research is implicated in the national race, particularly as questions of government scope and resources have factored in so highly. A group of 68 Nobel Prize winners endorsed President Obama recently, largely based on their view that Obama “delivered on his promise to renew our faith in science-based decision making and has championed investment in science and technology,” while concluding that Romney would “devastate a long tradition of support for public research and investment in science.”

Petition Filed for Supreme Court Review of Federal Funding for Embryonic Stem Cell Research

A petition for certiorari has been filed in Sherley v. Sebelius, the ongoing challenge to the NIH Guidelines for the federal funding of embryonic stem cell research funding (previous coverage). The recent decision from the Court of Appeals for the D.C. Circuit rejected the claim of the plaintiffs that the funding violates the Dickey-Wicker amendment, which prohibits the use of federal funds for any research in which an embryo is harmed or destroyed. That provision was interpreted by the court to not cover the process for deriving embryonic stem cells from embryos, thus not placing the NIH stem cell policy in violation of the funding ban. The challenging researchers continue to claim that such an interpretation is erroneous. In the D.C. Circuit decision, the concurring opinions acknowledged the murky legal climate for federal funding of embryonic stem cell research, noting the automatic attachment of the Dickey-Wicker amendment to HHS funding bills without much new deliberation since 1996. Judge Brown wrote: "Given the weighty interests at stake in this encounter between science and ethics, relying on an increasingly Delphic, decade-old single paragraph rider on an appropriations bill hardly seems adequate." The petition advances several procedural arguments against the D.C. Circuit’s decision; one alleges a violation of the Administrative Procedure Act (alleging the 2009 Obama Executive Order unlawfully relieved NIH from completion of its formal rule-making obligations) and a misinterpretation of the law of the case doctrine (does it include decisions made at the preliminary injunction stage?). The petitioners cite a conflict among the circuits over the law of the case doctrine, trying to entice the Court into a review. Before we hear from the Court on this petition, the upcoming election will intervene – and the contrasting positions of Obama and Romney will either uphold or dismantle the current NIH policy. There has been very little federal litigation on embryonic stem cell research, but we now have more than a decade’s worth of political instability over the issue, with another indirect political referendum on November 6th. It should be noted that the recent attempts at personhood legislation (also at the federal level) are contemporary initiatives to ban embryonic stem cell research, as they would codify the legal status of the embryo as a fully constitutionally-protected individual; that would likely outlaw embryonic stem cell research. A Romney victory could be expected to reverse the NIH policy and render this litigation moot; an Obama victory would not.

Appeals Court OKs Funding of Embryonic Stem Cell Research

The current legal challenge to federal funding of human embryonic stem cell (hESC) research continues (hESC litigation has been in the courts for several years), and a new appellate ruling on the merits of the challenge has been issued by the Court of Appeals for the D.C. Circuit. Embryonic stem cells are derived from embryos that may already exist (from, e.g., in vitro fertilization) or be newly created. The funding challenge was brought by several adult stem cell scientists who argue that NIH (National Institutes of Health) funding for hESC research violates existing federal law which prohibits the use of federal monies for any research in which embryos are destroyed (see here). The prohibition is found in the Dickey-Wicker amendment, first enacted in 1996. Now, the D.C. Circuit has reviewed a lower court’s ruling that the NIH funding did not violate the law, and it has upheld that decision. This ruling allows those engaged in hESC research to continue, and anticipate future funding opportunities from NIH. However, an appeal of this decision is likely, but beyond that, the politics of hESC research are still volatile and subject to the views of the governing executive branch. In the shift from the Bush to the Obama administration in 2009, the federal funding ban on hESC research was reversed by Executive Order 13503, and NIH is free to make grants for hESC research. Although stem cell policy issues are not  prominent in this year’s presidential campaign, there are pronounced differences between President Obama and Mitt Romney’s positions on stem cell research (Obama supporting embryonic stem cell research, while Romney focusing only on adult stem cell research), such that a GOP victory would likely ensure a return to the Bush-era restrictions on federal funding, while a Democratic win will keep the current policy. A recent article in the New England Journal of Medicine that examined the political climate for stem cell policies reported that 62% of those in a 2011 Gallup poll supported hESC research, suggesting that national support for such research could legitimize a more stable funding policy that reflected existing political consensus. However, federal funding for hESC research, generally interpreted ideologically as related to views on abortion, is likely to remain a political football in the U.S., with consequences for the stability of research plans and general optimism about the future of such research in American science. That volatility is costly.

Federal Court: Stem Cell Prep Is Subject to FDA Drug Regulation

In a case with ramifications for the emerging field of stem cell medicine, a federal district court has ruled that a stem cell preparation offered by a Colorado stem cell clinic met the classification of both a “drug” or “biological product” - and therefore subject to federal regulation by the FDA. The case posed the general issue of when a biotechnology-related procedure was no more than the practice of medicine – state and professionally-regulated – or whether the use of a novel biotech product (the stem cell preparation) triggers federal drug regulation as enforced by the FDA. In U.S. v. Regenerative Sciences (D.D.C. 2012), the FDA asked a court to order the company to stop performing the Regenexx stem cell treatment it offered to patients suffering from a number of musculoskeletal conditions, because it involved the use of an unapproved drug (stem cells). The procedure involved withdrawing bone marrow from a patient, extracting mesenchymal stem cells from the patient, and processing the cells to create a therapeutic preparation for injection to a site of interest, with a goal of restoring function to impaired joints. This is an “autologous” stem cell treatment – the patient’s own cells are used; immune rejection should be avoided. The FDA argued that the stem cell preparation used by Regenerative became a ‘drug”– subject to existing federal regulation by the FDA under the Federal Food Drug and Cosmetic Act (FDCA). The judge found that the interstate commerce requirements to invoke federal jurisdiction were met, as the stem cell preparation included an antibiotic that had been procured out of state. The judge rejected the argument of Regenerative that the procedures used to product the stem cell preparation constituted “minimal manipulation.” In contrast, the judge recited the techniques used to take the harvested cells from the patient and distill it down to the stem cell population, and regarded them as extensive enough to support the FDA’s argument that the stem cells met the “drug” classification. In addition, the judge also reviewed several FDA inspections of the facility which revealed a failure to comply with good manufacturing practices (GMP); such deficiencies supported the FDA’s further assertion that the Regenexx product was “adulterated.” Two definitional questions were posed in the case – were the stem cells a drug, regulated under the FDCA, and/or were the stem cells a biological product regulated under the Public Health Services Act (PHSA)? In both cases, the answer was yes. The stem cells performed as an “article” intended to impact patient health, and are also a biologically-derived product, subject to the separate requirements that such products must meet. Because the company had not sought FDA approval to use this product, the FDA sought a permanent injunction to stop Regenerative from offering the stem cell procedures, and it was granted. The company intends to appeal. This case provides a foundation for the FDA to assert its jurisdiction over many such clinics in the U.S. which are providing such services, using the FDCA. The FDA has been stepping up its oversight and investigations of stem cell clinics in the U.S.,  including the issuing of a 2012 critical report on Celltex, a Texas based stem cell clinic (where Gov. Rick Perry received treatment); the FDA found numerous manufacturing deficiencies that undermined the legitimacy of the claims made for its stem cell products. With this new ruling in hand, the FDA can now use the FDCA to target stem cell clinics where the treatment involves more than a “minimal manipulation” of biological materials – and it remains to be seen whether any of the treatments that use a patient’s own cells will meet that standard and escape the FDCA.

Legal Challenge to NIH Funding of Stem Cell Research Continues

The ongoing litigation that challenges the Obama administration policy on the funding of human embryonic stem cell (hESC) research continues this week, as the Court of Appeals for the D.C. Circuit heard arguments in the case. The debate over such funding occurs against the backdrop of the long-existing Dickey Wicker amendment which prohibits the use of federal funds for any research in which an embryo is destroyed. The lawsuit against NIH, brought by several adult stem cell researchers, allege that the federal funding sponsored by the Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) violates this existing funding prohibition. This funding followed the 2009 Obama Executive Order, which ended the Bush-era hESC funding ban. The current NIH Stem Cell Guidelines make note of the Dickey-Wicker funding restrictions, but reach the conclusion that its funding of hESC research does not violate them: "These guidelines therefore recognize the distinction, accepted by Congress, between the derivation of stem cells from an embryo that results in the embryo’s destruction, for which federal funding is prohibited, and research involving hESCs that does not involve an embryo nor result in an embryo’s destruction, for which federal funding is permitted." The guidelines dictate the proper sources for hESC: “hESCs derived from embryos created using in vitro fertilization (IVF) for reproductive purposes and no longer needed for these purposes, assuming the research has scientific merit and the embryos were donated after proper informed consent was obtained from the donor(s).” Thus, NIH is not endorsing the creation of embryos for the purpose of deriving embryonic stem cells, noting that “additional sources of human pluripotent stem cells proposed by the respondents involve complex ethical and scientific issues on which a similar consensus has not emerged.” An amicus brief filed by Coalition for the Advancement of Medical Research (composed of hospitals, universities, and patient advocates) and the Genetics Policy Institute, Inc., urged the court to rule for the legality of the NIH policy. No doubt, more uncertainty over the legal status of hESC research continues the climate of instability in which this research has been conducted, at least since the 2001 Bush administration policy that halted the use of federal funds for the creation of any new hESC stem cell lines. This policy was reversed in 2009 by President Obama, but the current litigation poses a direct challenge to its legality. Nonetheless, in the torturous route this litigation has taken, the fact that, in 2011, the D.C. Circuit had earlier declined to uphold a 2010 preliminary injunction against NIH (partly because of its view of the weakness of the plaintiffs’ case against NIH) would seem to indicate that the court will uphold the legality of the NIH funding policy. Nonetheless, hESC research is a political issue that will be affected by the outcome of the 2012 presidential race; the NIH funding policy is politically dependent on which political party controls the executive branch.

9th Circuit Rejects DOJ Challenge to Ruling on Stem Cell Donation

Technological advances can shift the legal characterization of a practice in medical care from prohibited to allowed – the case of compensation for bone marrow donation makes this point. Bone marrow donations are sought by many patients with blood and other disorders who require an infusion of new stem cells that can resupply critical blood types (bone marrow is a rich source of such cells). Typically, this has been done by bone marrow aspiration, where a donor undergoes aspiration of bone marrow directly, later processed for its stem cells; hence the term “bone marrow transplant” was often used. In Flynn v. Holder, the 9th Circuit ruled last December that the modern methods for recovering stem cells from bone marrow now allow for the procedure to be characterized as a kind of blood donation, rather than an organ donation; now, a donor goes to a facility and undergoes a kind of blood filtration to remove stem cells (peripheral blood stem cell apheresis), which is painless and non-invasive. The consequences of this shift are significant in that the the National Organ Transplant Act (NOTA), passed in 1984, prohibits any sale of human organs in interstate commerce. That legislation attempts to frustrate any markets for human organs by criminalizing the payments for human organ donations. In contrast, blood donations are not affected by this prohibition; payments for blood donations are routine. Thus, for the first time, the 9th Circuit ruling allows bone marrow donors to be paid; this has been championed by patient advocacy groups for those need genetically matched bone marrow. Surprisingly, after the ruling in December, Attorney General Eric Holder asked the court to rehear the case en banc (full panel of the 9th Circuit). This has now been denied. According to the court, the government’s argument that “bone marrow” in NOTA was to be understood to apply to the stem cells – however recovered – is not correct. The court has reaffirmed its ruling, and donors may be recruited with financial incentives without running afoul of NOTA. This is a wise decision; the pushback from the Department of Justice might be understood in view of what they may have viewed as a slippery slope toward the introduction of commerce into organ donation, but this apprehension does not require that the law fail to understand when technology really does shift. From the court opinion: 

It may be that “bone marrow transplant” is an anachronism that will soon fade away, as peripheral blood stem cell apheresis replaces aspiration as the transplant technique, much as “dial the phone” is fading away now that telephones do not have dials. Or it may live on, as “brief” does, even though “briefs” are now lengthy arguments rather than, as they used to be, brief summaries of authorities. Either way, when the“peripheral blood stem cell apheresis” method of“bone marrow transplantation” is used, it is not a transfer of a “human organ” or a “subpart thereof” as defined by the statute and regulation, so the statute does not criminalize compensating the donor.

9th Circuit: Bone Marrow Donation Technology Avoids Compensation Ban on Organ Donation

The 9th Circuit has ruled that the law which prohibits commerce in organ donation does not extend to modern techniques for hematopoietic (blood) stem cell donation. This is an important ruling which is likely to result in an increase in potential donors for blood stem cells. Flynn v. Holder challenged the applicability of the federal statute which prohibits compensation for organ donation to modern blood stem cell donation. The National Organ Transplant Act (NOTA), passed in 1984, prohibits any sale of human organs in interstate commerce. This has traditionally been interpreted to forbid any compensation for bone marrow donors. The treatment of many blood diseases, including cancers such as leukemia, involves the destruction of the patient’s own blood cells and replacement with blood stem cells from bone marrow provided by a genetically matched donor. (Note that this technology is unrelated to the controversy over embryonic stem cell research; this is a kind of adult stem cell donation). The plaintiffs included cancer patients seeking bone marrow stem cells and a bone marrow registry which intends to offer financial incentives for donations and to increase efforts to target ethnic groups that may be underrepresented in current banks. The plaintiffs argued that modern cell sorting technologies now allow the harvesting of hematopoietic stem cells directly from blood, and thus avoid the traditional procedure of bone marrow withdrawal to recover these cells. In essence, these technical advances mean that the donation of bone marrow stem cells can be accomplished through blood donation (which can be legally compensated) and no longer requires the painful and risky medical procedure of bone marrow aspiration (which could not be compensated). The distinction was critical to the analysis of whether the new stem cell donation technology avoids the label of “organ donation” and thus escapes the compensation ban. Several constitutional claims were also advanced. One claim was an equal protection claim which alleged unequal treatment of bone marrow as opposed to blood donations, arguing that compensation for renewable biological specimens is legal, and bone marrow should fall within that description. Another constitutional claim was rooted in a substantive due process claim of a violation of the right to seek medical treatment. The 9th Circuit avoided the constitutional questions, but decided that the modern blood-based method of stem cell donation did not qualify as an “organ donation” for which compensation is prohibited. One of the plaintiffs has announced the availability of scholarships and other financial remuneration to recruit stem cell donors, strategies that can now proceed legally, according to the 9th Circuit. 

Stem Cell Protagonists in Wisconsin Senate Race

The Wisconsin 2012 Senate race is featuring a particularly sharp contrast between the leading candidates regarding stem cell research, whether the stem cells are derived from existing adult cells or from embryos. The issue of embryonic stem cell research remains controversial as it requires the use of (and possible deliberate creation of) an embryo. Many “pro-life” advocates include an opposition to embryonic stem cell research as part of a platform which opposes the right to abortion. In the Wisconsin 2012 Senate race, former governor Tommy Thompson is the current frontrunner for the GOP nomination to run against Democrat Rep. Tammy Baldwin. Thompson has become not only an advocate, but a sponsor, of recent efforts to increase adult stem research. This was illustrated by his appearance last week at the adult stem cell conference convened by the Vatican, which has entered the stem cell debate through a 5-year, $1 million partnership with NeoStem, Inc., a New York-based adult stem cell biotech company. His remarks took aim at embryonic stem cell research in favor of promoting adult stem cell research: "That’s what I love about adult stem cells – we’re using the divine wisdom inside of us to supercharge our bodies and wipe away disease.  And as we do this, not one single human embryo is destroyed. " Here's an eyewitness report from Art Caplan of the University of Pennsylvania on the dubious scientific merits of the conference. Thompson has also called for a federal commission to be established that would specifically advance adult stem cell research.  Wisconsin Democrats have criticized Thompson's overt association with Vatican venture. Rep. Baldwin has been an advocate for embryonic stem cell research; of note is that one of the first successful efforts in isolating embryonic stem cells took place at the University of Wisconsin in 1998 and that Wisconsin has had a significant stem cell sector ever since. If Thompson secures the GOP nomination and Senate race is between Baldwin and Thompson, the stage could be set for a fairly explicit referendum on official policies toward adult vs. embryonic stem cell research. With Thompson standing with the Vatican efforts to elevate adult stem cell work and Baldwin being a firm proponent of embryonic stem cell research, this race would recast the stem cell debate in a novel and idiosyncratic context. Beyond the politics, what's important to remember is that research into both sources of stem cells is worth conducting and funding, but the scientific merits of each (and funding decisions to follow) may be interpreted through ideological filters which distort actual results. Thus, the relative merits of each may not emerge for years.

Mississippi's Ballot Initiative Would Confer Personhood on Fertilized Egg

The Mississippi Amendment 26 ballot initiative has attracted much attention. The amendment, up for vote on November 8th, establishes personhood for a fertilized egg, with the objective of ending abortions in the state and eliminating birth control options that interfere with the implantation of a fertilized egg. A similar ballot amendment was defeated twice in Colorado. If Amendment 26 becomes effective, its proponents note that “the Amendment would confer due process rights on the unborn.” Already, fetal homicide laws exist in at least 38 states. Such laws can effectively criminalize abortion. A useful commentary from Jessica Valenti summarized the various scenarios in which pregnant women who do not seek an abortion still can have their pregnancy-based health decisions affected, or prohibited by such laws. The scenarios for law enforcement include the prosecution of an Indiana woman charged with fetal homicide after a suicide attempt and a class of women charged under the Alabama chemical endangerment statute because of drug abuse during pregnancy, or the use of such laws in Mexico to prosecute Mexican women for miscarriages. Stem cell research advocates are also weighing in against Amendment 26, with Stem Cell Action noting that the attachment of legal rights to the fertilized egg would adversely affect embryonic stem cell research, access to in vitro fertilization (IVF) procedures, including interfering with the right of couples seeking to donate unused embryos for stem cell research. The Amendment, if passed, provides one more template for institutionalizing the unborn (fertilized egg, fetus) as a class of legal actors whose rights are set against established norms of reproductive autonomy for women, as well as against the scientific community that seeks to harness the power of embryonic stem cells for promising (but not necessarily imminent) therapeutic applications. Such laws also raise the specter of a diffuse spread of liability for many women (pregnant or not), medical professionals, and scientists.

European Court of Justice Prohibits Patenting of Embryonic Stem Cells

The European Court of Justice (ECJ) issued its opinion in an appeal from a German court decision regarding the patentability of embryonic stem cells (ESC). Originally, Greenpeace challenged the grant of a German patent on a method for deriving neuronal progenitor cells from ESC, and achieved a favorable ruling from the Federal Patent Court of Germany. That court then referred the overarching policy question on the granting of such patents to the European Court of Justice in view of the Directive 98/44/EC of the European Parliament (the legal protection of biotechnological inventions). This EU-wide directive sets out the standards for patentable subject matter. First, the directive establishes the concept of public morality as a touchstone for patenting decisions (the U.S. lacks any such standard). Article 6.1 of the Directive notes that “Inventions shall be considered unpatentable where their commercial exploitation would be contrary to ordre public or morality” while Article 6.2 prohibits the “uses of human embryos for industrial or commercial purposes.” The court’s summary states that “the use of human embryos for purposes of scientific research which is the subject-matter of a patent application cannot be distinguished from industrial and commercial use and, thus, avoid exclusion from patentability.” This decision firmly halts most patenting efforts in the EU on ESC technologies. Contrast this outcome with the ban on federal funding of ESC research instituted in 2001 by the Bush administration. That was not a patenting decision, but it had great effect on reducing incentives and opportunities for U.S. stem cell research. That ban has since been lifted (see here). While patenting opportunities are limited in the EU, U.S. patenting remains available, and one of the consequences of the ECJ decision will be to offer the possibility of evaluating the costs and benefits (incentives, or lack of) for two sharply contrasting IP environments for ESC research.

Is it Real Progress to Personalized Stem Cells?

A reported advance from the New York Stem Cell Foundation in deriving stem cells from cloned embryos is attracting much attention. Here’s the research paper. The researchers were able to transfer a nucleus from a donor cell into an oocyte which retained its nucleus, and get the oocyte to develop into blastocyst level (70-100 cells), from which they extracted stem cells, which would now be embryonic stem cells (ESC).  What’s notable is that this technique of somatic cell transfer leading to stem cell development and harvest had not worked to date with human eggs. That explains much of the attention that this report is generating. However, the catch here is that the researchers found it necessary to maintain the oocyte nucleus while adding in the new nucleus – so the stem cells have extra chromosomes (3 times normal), and are abnormal. It's important to note that the ability to transfer a new nucleus to an existing egg and cause embryo development is the precursor to the long-sought ability to create personalized stem cells. But this report does not put us there. Many of the mainstream news reports oversell the scientific impact here, both reporting it as an unfortunate advance toward the possibility of  human cloning, and a fortunate advance toward producing customized stem cells. Both alarm and hope are triggered, out of proportion to the actual results. It’s worth, noting, however, because the public sense of how science is proceeding can translate into demands for oversight or access; thus demands for legislative attention (see, e.g., 1997 Dolly sheep cloning-inspired legislative flurry, see here for an updated list of state cloning laws, and note the origin of such efforts in 1997, when the cloned sheep was revealed). No federal legislation has been enacted, although President Clinton did issue an executive memorandum at the time banning the use of federal research funds for human cloning; in addition, the FDA maintains its authority to regulate any such attempts.

Appeal Filed in Ongoing Embryonic Stem Cell Funding Litigation

An appeal has been filed in the ongoing challenge to the government's policy of providing funding for embryonic stem cell research (ESCR).  This funding followed the Obama Executive Order in 2009, which ended the Bush-era ESCR funding ban.  Several adult stem cell researchers allege that the federal funding sponsored by the Department of Health and Human Services and the National Institutes of Health (NIH) violates the existing Dickey-Wicker amendment, which prohibits the use of federal funds for any research in which an embryo is destroyed. The NIH Stem Cell Guidelines, published in 2009, reference the amendment, but make it clear that the ESCR research does not violate it:  "These guidelines therefore recognize the distinction, accepted by Congress, between the derivation of stem cells from an embryo that results in the embryo’s destruction, for which federal funding is prohibited, and research involving hESCs that does not involve an embryo nor result in an embryo’s destruction, for which federal funding is permitted."  The plaintiffs had won a preliminary injunction against the research in August 2010. In April, the appellate court lifted the injunction, finding that NIH was likely to prevail against the challenge, effectively upholding the research funding, stating that the term "research" in the amendment was ambiguous. The lower court then ruled against the challenge.  This appeal continues the back and forth litigation on this issue; the D.C. Circuit has certainly signaled its pro-ESCR reading of the Dickey-Wicker amendment, and could be expected to maintain this view in the merits challenge now filed.  Reports are that NIH spent around $200 million on ESCR-related research in 2010.

Stem Cell Decision in Federal District Court

In the ongoing dispute over whether embryonic stem cell research can be supported with funds from the federal government, a federal district court has ruled that the National Institutes of Health (NIH) can fund this work. The District Court for the District of Columbia issued its ruling in a challenge by two researchers opposed to the policy. The plaintiffs had argued that the existng Dicker-Wickey amendment, passed by Congress in 1995, which prohibits the funding of “research in which a human embryo or embryos are destroyed” should be interpreted to exclude embryonic stem cell research. The court disagreed, reasoning that NIH had the discretion to characterize the stem cell research as distinct from any research in which embryos are actually destroyed, thus avoiding the Congressional prohibition. Stem Cell Decision Dist. D.C. 2011

Clinical Trials of Human Embryonic Stem Cells Expand

We are seeing the era of full clinical evaluation of stem cell therapies unfold. This week brings an announcement by Advanced Cell Technology in California that the FDA has approved two more clinical trials using human embryonic stem cells (hESC) for retinal transplantation in patients with severe opthamalogic disease. In the laboratory, the stem cells were differentiated into retinal cells. The cells are transplanted, and these initial infusions will asses safety and tolerability of the cells in these individuals. The first FDA-approved clinical trial of hESC was announced last fall by Geron in which the stem cells were differentiated into neuronal cells and transplanted into patients with spinal cord injury, in an attempt to restore motor activity and induce nerve repair. The clinical trials began with the FDA approval of the Geron trial in January, 2009, just after the start of the Obama administration, which had vowed to lift the Bush-era restrictions on research into hESC. An Executive Order was issued in March, 2009, which did exactly that, unambiguously:

For the past 8 years, the authority of the Department of Health and Human Services, including the National Institutes of Health (NIH), to fund and conduct human embryonic stem cell research has been limited by Presidential actions. The purpose of this order is to remove these limitations on scientific inquiry, to expand NIH support for the exploration of human stem cell research, and in so doing to enhance the contribution of America’s scientists to important new discoveries and new therapies for the benefit of humankind.

The full determination of the clinical promise of hESC therapies (or those derived from adult stem cells) will take years. But the field certainly cannot contend with an erratic regulatory climate and unsettled expectations, which is what has happened for nearly a decade.