Fetal Tissue Research: Enduring Controversy, New Contexts

 

Videos released in 2015 by the anti-abortion Center for Medical Progress (CMP) ignited a storm of controversy regarding fetal tissue research (FTR): the use, in various forms of biomedical research, therapeutics, and vaccine production, of tissues and organs from fetuses whose lives were ended through induced abortion.[1] The videos and associated CMP material, which alleged a pattern of commodification of human fetal tissue (HFT)[2] by Planned Parenthood, HFT brokers, and research institutions, prompted a Congressional investigation;[3] in turn, Planned Parenthood and supporters of FTR in science, pharmaceutical manufacturing, and politics decried CMP’s undercover investigation as deceptive and harmful to life-saving medical research.[4] A civil lawsuit by Planned Parenthood resulted in a judgment against CMP in excess of $2 million,[5] and CMP’s leaders face ongoing criminal prosecution for illicit recording of “confidential conversations”—prosecutions the Los Angeles Times, in an editorial otherwise dismissive of CMP’s work, castigated as “disturbingly aggressive.”[6]

Whatever one may think of CMP’s tactics, the videos raised disturbing issues, as acknowledged by a prominent Planned Parenthood-sympathetic journalist.[7] More important, its work prompted a long-overdue public reconsideration of the tenuous ethical and legal framework, established three decades ago in the United States and Europe, allowing FTR. The United Kingdom’s Polkinghorne Report (1989) noted that such reconsideration would be necessary: “It is desirable that subsequent revision should be undertaken as it becomes necessary and not have to wait until the arousal of considerable public concern before being taken in hand.[8]

The CMP controversy illustrates the consequences of having awaited the arousal of such concern; the ensuing debate predictably generated more heat than light, and dispassionate reappraisal of the ethics and justifications for federal funding of FTR was virtually absent from public debate. For example, claims that Planned Parenthood and other abortion providers “broke no laws” in their collection and provision of HFT spoke more to the lack of appropriate regulation and oversight of such practices than to their actual legitimacy. Moreover, questions of legal liability are subordinate to the ethical questions inherent in FTR—rooted in the unresolved debate over the moral status of the human fetus—as well as those arising from the commodification of HFT as a “tool” for researchers.

This essay provides background for the reconsideration of these critical questions set forth in this Special Report. We begin by examining the factual assumptions and ethical analysis that led authorities in the United States and Europe to conclude that the beneficial use of HFT in research could be “ethically isolated” from the disputed morality of abortion. After a brief review of federal and state law on FTR, we then turn to highlight the findings of the Congressional investigation launched in the wake of the CMP videos, which clearly demonstrated the insufficiency of current laws and regulatory oversight to ensure that the process of maternal consent for HFT donation conforms to generally applicable standards for medical research and to preclude the development of commercial markets in HFT. The final section briefly addresses the current controversies regarding 2019 revisions to the National Institutes of Health (NIH) guidelines for funding of FTR and the use of FTR in the development of vaccines for SARS-CoV-2.

I. “Ethical Boundary-Work”: The Precarious Consensus Validating Fetal Tissue Research

Biomedical research employing HFT from multiple sources, but primarily from induced abortion, has been conducted for a century. Early efforts at HFT transplantation to treat Addison’s disease, cancer, and diabetes yielded no widely applicable clinical benefit. In the decades between 1960 and the mid-1980s, the medical literature reported various cases of fetal tissue transplantation with “dismal” clinical results and patient survival rates that may have been caused by poor research design and the absence of preclinical animal research.[9] However, FTR contributed to the Nobel Prize-winning research of John Enders, Thomas Weller, and Frederick Robbins, who established the ability of the polio virus to grow in cultures with various types of tissues. While HFT was not (and is not currently) used in the production of the polio vaccine, these discoveries made possible the propagation of sufficient quantities of the virus for vaccine production, as well as enabling the growth of other significant viruses.[10] In addition, descendent cell lines from a small number of fetuses aborted in the 1960s and 1970s led to development and current production of the rubella vaccine and are currently used in the production of vaccines for several other viruses.[11]

The expansion of FTR to a broader array of research was made possible only by the widespread legalization of elective abortion in the United States and Europe starting in the 1960s. Only at this point was there an adequate supply of HFT to maintain tissue banks and meet the demands of researchers. As a network of European researchers noted in 1994, their studies “depend heavily on the availability of human embryos and fetuses and therefore gain momentum from the occurrence of elective abortions.”[12] Accordingly, despite efforts to claim that the ethics of FTR could be separated from the controversy over abortion, the issues remain pragmatically, ethically, and legally intertwined. Without widespread elective surgical abortion, sufficient HFT for new research would not be available; however, the “moral aspects” of reliance on induced abortion require ethical guidelines and regulation beyond those applied to the general donation and research on cadaveric human tissue.[13]

Such guidelines play a pivotal role in the “ethical boundary work” that accompanies the emergence of controversial innovations in biomedical research, such as FTR and embryo research.[14] While research scientists ought to be responsible for the exercise of their own moral agency, in practice, the approbation and regulation supplied by outside authorities allows researchers, as long as they act within those guidelines, to sequester their personal qualms about the ethical boundaries of their work.[15] The research community obviously has input into such guidelines, but once they are established, “research ethics” becomes a matter of regulatory compliance. Wainwright et al. note, “Scientists thereby become responsible for pursuing the ethically valuable ends of helping people through research, whilst concurrently being ‘non-responsible,’ through allowing regulating authorities to ensure their ethical accountability.”[16] As we will see, where regulating authorities fail in that regard, the work of establishing ethical boundaries suffers accordingly.

In the United States, such guidelines first emerged over 30 years ago, incited by controversy over the use of HFT in transplantation research aimed at ameliorating the effects of Parkinson’s Disease and other neurological impairments. The Department of Health and Human Services (HHS) placed a moratorium on federal funding of such research in March 1988; nine months later, a 19-member NIH Human Fetal Tissue Transplantation Research Panel, headed by retired federal judge Arlin Adams, concluded (with four dissents) that the funding moratorium should be dissolved. The panel majority concluded, inter alia, that consent for donation of fetal tissue could be obtained in an ethical manner from the woman seeking the abortion as long as that consent was kept separate, to the extent possible, from her consent to abortion.[17] Responding to objections from the panel’s dissenters, the majority concluded that the mother “still has a special connection with her fetus” and thus a legitimate interest in the disposition of the fetal remains.[18] Further, while acknowledging the possibility that using HFT in research and transplantation might constitute an incentive for an ambivalent woman to proceed with an abortion, the panel concluded that this should not be considered a “prohibited inducement.”[19] And, while conceding that it is “of moral relevance” that HFT has been obtained from induced abortion, “a decisive majority of the panel found that it was acceptable public policy to support transplant research with [HFT] either because the source of the tissue posed no moral problem or because the immorality of its source could be ethically isolated from the morality of its use in research.”[20]

The claim of “ethical isolation,” further defended in a separate statement by John A. Robertson, joined by 10 other members of the panel, rested on three basic premises:

  1. that the prospect of HFT donation would be a negligible incentive for women considering abortion, and likewise not impact societal acceptance of abortion;[21]
  2. that those who conducted or obtained the benefits of HFT transplantation research bore no moral complicity in the act of abortion;[22] and
  3. that HFT “can be obtained and distributed for research use without close involvement in the abortion process.”[23]

Regarding the first point, the Robertson statement tellingly referred to “family planning abortions,” which occur disproportionately among minority and economically disadvantaged women.[24] Having prescinded from considering the morality of abortion, the panel also did not address how the circumstances of women seeking abortions might affect its assertion that strict separation could be maintained between the decisions to abort and to donate HFT.[25] The first premise thus was defended on the basis of procedure: a pregnant woman has previously consented to an abortion and, in an ostensibly separate decision, consents to donation of what will become—but is not yet—the cadaveric tissue of her unborn child. Yet even here, the principle of isolation is subordinated to utilitarian concerns. “Ideally,” the panel majority wrote, consent for donation “would not even be sought” until after the abortion occurs. However, because post-mortem tissue deteriorates rapidly, “the pregnant woman must be consulted before the abortion is performed” and may even at that time agree to procedural options that would make the HFT more useful for research or therapy.[26]

Regarding the second premise, the Robertson statement declared that issues of moral complicity will only matter to those morally opposed to abortion. Without discussion of or even citation to the extended literature on the subject of moral complicity in evil, the statement asserted that “a researcher using tissue from an elective abortion is not complicitous with the abortionist or the woman seeking abortion.”[27] It further asserted that those who engage in FTR despite such moral qualms “surely are not corrupted because they choose to salvage some good from an abortion that will occur regardless of their research or therapeutic goals.”[28] This assumes, however, that such persons are amenable to consequentialist justifications as a means to appease their moral conflicts. In fact, their conscience militates against such justifications precisely because they are viewed as corruptive of non-negotiable moral norms, and, in this case, because accepting such justifications can lead to further desensitization to the evil of abortion.[29]

These foundations, in turn, rest on the shaky ground stated in the third premise, that researchers will have no close connection to the abortion process. The Robertson statement rejected the dissent’s assertion that FTR would “institutionalize a [federally funded] collaboration with the abortion industry” in which aborted fetal remains “become a regularly supplied medical commodity.”[30] Such claims are misleading, the statement asserts, because “independent tissue agencies” will make the transfer of otherwise-wasted fetal remains available for research.[31] The statement’s assumptions were invalid at the time due to clear evidence of the close relationships needed to procure neural HFT for transplantation; the passage of time only further demolished them. As the next section will detail, abortion clinics, tissue-procuring “middlemen,” and researchers often worked in close collaboration to secure the consent of pregnant women to tissue donation and to ensure that the particular tissue donated met specific research needs. As the Panel’s dissenters predicted, HFT has indeed become a research commodity with specialized market demands, casting serious doubt on the Panel’s claim of “ethical isolation” from abortion.

Seven years after the NIH Panel delivered its report, a network of European transplant researchers (NECTAR) published a set of “self-imposed ethical guidelines for the use of human embryonic and fetal tissue for scientific and therapeutical purposes, including their rationale.”[32] The NECTAR guidelines, while reaching many of the same conclusions as the NIH Panel, provided a significantly more detailed analysis of the scientific and ethical issues at stake in FTR, and thus a stronger (if not ultimately persuasive) justification for the continuation of such research. While space does not permit a detailed analysis of NECTAR’s findings, its treatment of informed consent highlights a significant gap in the NIH Panel’s guidance and a major flaw in the practice of obtaining consent for HFT donation that emerged in the United States. NECTAR proposed that the specific purpose(s) for which the donated HFT might be used should be made clear as part of the consent process; it firmly rejected the position taken by the UK’s Polkinghorne Report that consent should be general and cover all the possible ways in which embryonic or fetal tissue could potentially be used. This position, according to NECTAR, “does not take into account the fact that some women may give permission only for a particular application and not for any other,” giving as an example a woman who would approve of research into prenatal development “but be horrified at the prospect of its use for implantation in laboratory animals.”[33] The NIH Panel failed to address this issue at all, and as Congressional investigators documented, consent forms used in the United States give “carte blanche” permission for any use of donated HFT.

For its part, the UK’s Polkinghorne Report asserted that “carte blanche” permission was essential to enforce the “principle of separation” between FTR and the woman’s decision to abort. To further secure this principle, the Report’s guidelines require that consent for HFT donation must be sought by an intermediary who is neither a member of the abortion clinic or hospital staff nor employed by the research team, and the salary of the intermediary represents an additional expense. However, the intermediary depends on the clinic or hospital staff to screen patients who might be suitable candidates to give such consent, and in the process of obtaining consent, informal disclosure of the research purposes for HFT are sometimes disclosed to the woman.[34] These strictures on consent, which one critic blames on undue deference to the concerns of pro-life advocates, may have made it more difficult for British investigators to obtain HFT.[35]

However, while a “fetal tissue economy” has emerged in the UK—an unavoidable circumstance given the exchange relationship between the woman who has an abortion and those who use the corporeal remains of the fetus for research—that economy is far more regulated than in the United States, and there are no published reports of the types of abuses in procurement and marketing of HFT such as those uncovered in the Center for Medical Progress videos. Nonetheless, as noted 30 years ago by John Keown, the Polkinghorne Report suffered from the same fundamental deficiency as the NIH Panel: failure both to deal consistently with the moral status of the fetus and to satisfactorily address the moral complicity of researchers in using HFT from abortions obtained purely for family planning or social purposes.[36]

II. Failure of Regulation: The Findings of the House Special Investigative Panel

In 1993, Congress codified the recommendations of the NIH Panel,[37] not only permitting federal funding of FTR but also specifically barring HHS from imposing a moratorium on human fetal tissue transplantation research.[38] Federally funded research must comply with state laws, and procurement of HFT must meet certain standards: the “woman providing the tissue” must give informed consent and may not know the identity of the potential transplant recipient; such consent must be obtained after consent to the abortion has been given; and the physician performing the abortion must certify that no alteration of the timing, method, or procedures used to terminate the pregnancy was made solely for purposes of obtaining HFT.[39] HHS compliance audits must be kept confidential. Finally, of particular relevance to the claims presented by the CMP against Planned Parenthood and others, it is a federal crime “for any person to knowingly acquire, receive, or otherwise transfer any human fetal tissue for valuable consideration if the transfer affects interstate commerce.”[40] However, this prohibition does not extend to “reasonable payments associated with the transportation, implantation, processing, preservation, quality control, or storage” of HFT; the criteria for establishing “reasonable” level of payment were not defined.[41] Moreover, once HFT is cultured into stem cell lines, implanted in laboratory animals, or otherwise converted, it no longer constitutes “human fetal tissue,” and the law imposes no restraints on the commodification or marketing of such products.[42]

Other federal laws and regulations applicable to FTR include the 1981 “Common Rule” for research projects receiving federal funding.[43] The Common Rule requires informed consent on the part of any human research subject, review of proposed research by an Institutional Review Board, and written assurance of compliance from the institution conducting the research. The Privacy Rule implemented under Health Insurance Portability and Accountability Act of 1996 (HIPAA) protects personal health information from disclosure.[44] Finally, at the state level, a patchwork of laws largely replicate the federal ban on the commercial sale of fetal tissue and ban experimentation (as does federal law) on living aborted fetuses. However, a handful of states ban FTR outright.[45]

The CMP videos sparked a Congressional investigation into whether the current practices of abortion clinics, tissue procuring organizations (TPOs), and researchers violated any of these legal strictures. A Special Investigative Panel chaired by then-Rep. Marsha Blackburn documented the commodification of HFT and its derivative product, as well as the emergence of complex economic arrangements among abortion providers, TPOs, and researchers, thus vindicating many of the concerns raised by critics of FTR 30 years earlier.[46] Among the Panel’s key findings were the following:

  • Over the years four business models emerged to meet researchers’ demand for HFT: (1) the “middleman model,” in which a TPO obtains fetal tissue from an abortion clinic, preserves and transfers it, at a profit, usually to university researchers; (2) the “university/clinic model,” in which university researchers establish a direct relationship with an abortion clinic to ensure a regular supply of HFT; (3) the “biotech company/clinic model,” in which the biotech company establishes the direct relationship to the clinic; and (4) the “late-term clinic model,” allowing for the recovery of more mature fetal tissues, organs, and cadavers.[47]
  • To obtain “informed” consent for fetal tissue donation, abortion clinics (including Planned Parenthood) and TPOs drafted forms claiming that FTR has been used to find a cure for diseases such as diabetes, Parkinson’s, Alzheimer’s, cancer, and AIDS—which a leading fetal tissue researcher acknowledged were misleading, as no cures using HFT have been found for these or any other disease.[48] Witnesses from Planned Parenthood also conceded that the form is inadequate.[49]
  • To expedite the collection of HFT, TPOs typically embedded technicians within abortion clinics; these technicians would receive orders each day to collect certain forms of tissue or organs at specified levels of fetal gestation.[50] To meet these orders they would gain access to patients’ personal health information, creating a possible violation of the HIPAA Privacy Rule, and then select specific patients from whom to obtain consent using the misleading forms described above.[51]
  • University-based researchers either purchased HFT from such TPOs or embedded their own technicians directly in abortion clinics. The University of New Mexico used such a relationship to expand its own abortion services, providing physicians to perform abortions and training others to do so, while extending faculty status to abortion doctors. It also employed a single form to obtain consent for both abortion and fetal tissue donation, and in some cases did not inform women that the fetal remains would be donated for research.[52] The University of Washington, home to the nation’s largest HFT bank in its Birth Defects Research Laboratory, obtained tissue from a dozen abortion clinics. One such clinic promised women that “only fetal tissue and stem cells can further birth defects research” and that HFT is being used to regenerate spinal cells so paralyzed people can walk someday.[53]
  • Fetal tissue research’s importance, the Panel concluded, is far less significant than claimed in these consent forms. From 2010 to 2014, NIH grants for FTR comprised 0.2% of its total grant disbursements. Of the 298 grants for FTR, the vast majority went to research for HIV/AIDS (74), vaccine research (28), and a variety of neurological disorders, including Zika virus research (158). Placing these numbers in further perspective, the 158 grants for brain-related FTR accounted for 0.3% of the total grants for neurological research (52,338), and those for AIDS research 1.5%. There was no NIH funding for FTR research involving Alzheimer’s, ALS, or spinal cord injury, and negligible funding for a range of other diseases.
  • Looking further at published research and active clinical trials, the Panel concluded that “fetal tissue research is outdated technology that is largely ignored” in clinical research.[54] Based on the government’s database, the Panel found that FTR was involved in only 42 of 230,000 clinical trials worldwide. The panel concluded that despite FTR having been employed since the 1920s, “not a single clinical treatment has been developed from human fetal tissue.”
  • Regarding vaccines, the Panel acknowledged that the rubella vaccine is an “isolated case” where descendent cell lines from fetuses aborted in the 1960s and 1970s are used in current production, because the viral strain isolated from these cell lines is effective in eliciting a strong immune response. However, the Panel contested claims that FTR or descendent fetal cell lines are essential in current vaccine manufacture, or that they were essential to initial vaccine development. Of 75 vaccine formulations then approved by the Food and Drug Administration, only 11 are produced using descendent cell lines, and in only 5 cases (vaccines against adenovirus, hepatitis A, rubella, varicella, and zoster) are there no alternative vaccines available. The Panel further contended that all of these vaccines could be produced without using the descendent cell lines, although it also acknowledged that using new methods of vaccine generation would require new FDA approval, a labor-intensive and costly process.[55] Thus, while claiming that current modes of manufacture are “outdated,” the Panel implicitly recognized that in these limited cases descendent cell lines would continue to be used.
  • Several research institutions, mostly university-based, submitted claims to the Panel that HFT was necessary for the study of human development, particularly neurological development and related impairments, including Down syndrome and those brought about by maternal exposure to the Zika virus. Consistent with its findings regarding NIH research grants, clinical trials, and vaccine production, the Panel noted that a very small percentage of peer-reviewed studies on neurogenesis involved HFT, and that promising research into a vaccine for Cytomegalovirus, which can also cause serious neurological deficits in children, does not involve FTR at all.[56]

Political controversy has largely prevented any even-handed assessment of the Panel’s Report, and space permits only a brief assessment here. The Panel’s primary achievement, in retrospect, was to provide long-delayed oversight into the implementation—and sufficiency—of the 1993 legislation authorizing and regulating federal funding for FTR. Its findings clearly established that federal regulation since 1993 had failed to ensure the integrity of the process of informed consent given for HFT donation, to ensure that such consent is not obtained by parties with a vested interest in the women’s decision whether or not to donate, to safeguard personal health information, or to prevent either the close collaboration of research institutions and abortion providers or the emergence of profitable markets in HFT. The Panel also exposed the illusory nature of the “ethical isolation” between abortion practitioners and HFT researchers promised by the 1988 NIH Panel by documenting the practice of embedding TPO and university research personnel in abortion clinics, and the pattern of bespoke orders for fetal tissue and organs of particular gestation. Furthermore, its findings on the commodification and profiteering in HFT echo those of other commentators, fully supportive of legal abortion, who have criticized the exploitation of abortive women in the “fetal tissue economy.” Despite strident criticisms of its work, its findings regarding TPOs DaVinci Biosciences and DaVinci Biologics coincided with those of the Orange County (CA) district attorney, who later obtained a $7.8 million civil settlement against these entities for illegally profiting from the sale of HFT and stem cells.[57] (Notably, for years both companies had procured fetal tissue from Planned Parenthood abortion clinics.)

As a result of the Panel’s investigation, TPO StemExpress terminated its relationship with Planned Parenthood and apparently no longer includes HFT among its research products.[58] Another TPO, Advanced Bioscience Resources, was found by the panel to have paid $328,000 to California Planned Parenthood affiliates for fetal tissue specimens and to have violated other procurement requirements for HFT; the FDA in 2018 terminated a small contract with Advanced Bioscience Resources to provide fetal tissue for testing protocols.[59] Finally, Planned Parenthood affiliates ceased charging for providing HFT to researchers and TPOs, potentially mooting the Panel’s and CMP’s charge that Planned Parenthood affiliates illegally profit from their relationships with TPOs and researchers.[60] The Panel made multiple criminal referrals to state and federal authorities; even if these referrals did not result in prosecutions, the identification of potential legal violations can be presumed to have had at least some deterrent effect. Finally, despite their often-polemical disagreements, the Panel’s majority and minority also reached common ground on several issues, including that no one should profit from the sale of HFT, that some existing fetal tissue donation consent forms made inappropriate claims regarding outcomes from FTR, and that to date, no cure for any disease had been found using HFT.[61]

The Report can be faulted, however, for its overly polemical rebuttal of claims from researchers and the Panel’s Democratic minority that FTR is necessary for progress in research for vaccines and treatments for neurological impairments, HIV/AIDS, and diabetes.[62] The Report ably demonstrated that FTR constitutes a relatively insignificant portion of government-funded and published research. Furthermore, its stated objective—“to determine how best to support science” so that important research “can advance as rapidly as possible without ethical compromise”—was laudable and clearly a proper subject for Congressional oversight. However, the Report’s 400 pages included no rigorous assessment of the specific properties of HFT that have led to its use in research and attempted clinical treatment. It is well established that HFT’s unique capacities for cell proliferation and differentiation, at least before the advent of stem cell technology, could not be found in other human biologic materials.[63] The Report’s assent to research using fetal tissue from spontaneous abortion implicitly concedes that HFT could have some beneficial research purposes, even at the present time.[64]

The Report’s accusation that past research using HFT is “no more relevant to the practice of modern science than vacuum-tube technology is relevant to modern television manufacturing,” besides drawing a clumsy analogy, overlooks the fact that it is the very properties present in HFT that scientists now hope to find using stem-cell technology.[65] The Report’s further criticism that scientists who claim “speculative” future benefits of FTR are “no more capable of predicting the future than anyone else” can be applied to all primary researchers in any scientific endeavor.[66] In an effort to further denigrate the value of all FTR, the Report asserted that had John Enders and his colleagues used monkey cells in an attempt to grow the polio virus before they used HFT, they still would have made their groundbreaking discoveries regarding the properties of the polio virus and would still have won the 1954 Nobel Prize.[67] However, Enders’ discovery regarding polio virus was secondary to his effort to grow varicella virus in tissues from aborted embryos. For unclear reasons, polio virus was injected into some HFT cultures that were not used in the varicella experiment, where they “grew spectacularly.”[68] The Report thus got things backwards. The Enders laboratory was not primarily focused on efforts to grow polio virus; rather, through its efforts to grow other viruses in various cultures, human and animal, it fortuitously discovered the replicative properties of polio in non-neuronal tissue.[69] At some point, the Enders laboratory or others would have discovered these properties of polio using tissue cultures from other sources, but polio-specific research efforts to that point had been unavailing. Fortuitous or not, HFT cultures did play a pivotal role in Enders’ timely discovery.

Finally, in dismissing the potential importance of FTR in vaccine research for the Zika virus, the report claims that, because FTR is not currently being used in vaccine research for Cytomegalovirus (CMV), it need not be used in Zika virus research.[70] However, the fact that Zika and Cytomegalovirus both can cause similar devastating neurological impairments in newborns does not establish a close biological relationship between the viruses or that the path to success in either research endeavor will proceed along similar trajectories. Again, the Report validly noted that in the case of federally funded Zika research, relatively few grants support FTR. But the Report’s excessive rhetoric diminished the force of its overall argument that the putative need for HFT in biomedical research is diminishing with progress in stem cell technology, especially the emergence of ethically uncontroversial induced pluripotent stem cells.[71]

Despite these lapses, the Report clearly established the need to reassess whether the claimed benefits of FTR justify further federal funding. The trajectory of HFT transplantation research—at the center of the FTR debate 30 years ago—further illustrates the need for such reassessment. The promise of HFT transplantation in that period was based on a limited series of studies, notably in Sweden, showing some improvement in Parkinson’s disease patients who had received neural transplants of fetal tissue.[72] However, efforts to replicate this research resulted in multiple failures, some of them catastrophic, and no consistent explanation for why treatments worked in some cases and not in others.[73] Researchers placed a self-imposed moratorium on using fetal tissue for neural transplantation that lasted from 2003 to 2014.[74] Neural transplant regimens also require a particularly close reliance on specific methods of abortion, compromising the principle of separation set forth in the NIH, Polkinghorne, and NECTAR guidelines. Since each transplant attempt required tissue from as many as four aborted fetuses per transplant,[75] researchers recognized early on that the demand for such treatments, even if proven to be clinically successful, could not be met by the existing supply of fetal tissue from abortion and that alternatives must be found.[76] Hence, the very research that was championed in order to oppose the 1988–1993 ban on federal funding of FTR was, as a practical matter, never suited for widespread clinical treatment of Parkinson’s disease patients.

This history should be an object lesson against promotion of the potential benefits of ethically controversial research. Combined with the findings of the House Special Panel regarding abuses in the procurement of HFT, the time had come for reassessment of ethical and legal “settlements” reached in the last century. Moves by the Trump Administration, coupled with the worldwide search for a vaccine for SARS-CoV-2, have again brought the FTR controversy to the forefront of scientific, ethical, and public debate. A brief concluding section will trace these developments.

III. A Path Forward: FTR in the Age of Stem Cells and Advanced Virus Research

In June 2019, the Trump Administration announced reforms of the NIH grant review process that follow many of the recommendations of the House Panel Report. Intramural FTR by NIH scientists was banned, although research may continue using existing descendent cell lines.[77] David Prentice’s essay in this report reviews both the history of the grant review process established by these reforms, as well as the impact of the termination of that review process by the Biden administration.[78] Suffice here to note that the 2019 reforms, some of which remain in effect (including a revised grant application form that emphasizes procedures for identifying, budgeting, and justifying the use of fetal tissue derived from abortion) constitute the first significant effort to regulate the “FTR economy” in the United States.[79] Thus, we can conclude that despite (or perhaps because of) the controversy it engendered, the report of the Congressional Special Panel resulted in at least nominal reform of those aspects of the FTR economy funded by the NIH.

The SARS-CoV-2 pandemic opened a new chapter in this controversy, but one involving an old issue: the use of HFT and immortalized cell lines (such as HEK293) in vaccine research. In assessing this ongoing debate, one that is likely to be repeated as new pathogens emerge in future years, it is critical to draw a distinction between the types of research and vaccine production that may (or may not) involve ethically controversial FTR or use of immortalized cell lines.

For example, some researchers claim that FTR involving the creation of “humanized mice”—using HFT (in particular, fetal liver tissue) to replace the immune system in immunodeficient mice—is essential to current vaccine research.[80] However, a 2018 comparative study of the use of humanized mice in research acknowledged that ethical limitations curtail the supply of fetal tissue and that advances in induced pluripotent stem cell technology would be a solution.[81] In 2020, NIH researchers reported in a pre-peer-reviewed study the creation of the first human immune system humanized mouse model, the immune system being reconstituted using stem cells derived from human cord blood.[82]

In contrast to the use of newly obtained fetal tissue in vaccine research, the use of immortalized cell lines initially derived from fetuses aborted in the twentieth century presents a more complex problem. Under the umbrella of Operation Warp Speed, the NIH provided substantial funding for SARS-CoV-2 vaccine research, some that involved production using these descendent cell lines and some that did not. Various religious leaders and ethicists opposed to elective abortion called for equitable funding for research that did not employ these cell lines. While some commentators argued that the production or use of vaccines produced using the cell lines is always unethical, the prevalent view among commentators opposed to abortion was more reserved, opposing in principle the production or use of vaccines derived from the cell lines but also noting that given the remoteness of any possible complicity in the long-ago abortion, and the grave need to achieve widespread immunity from the virus, no one is morally obliged to reject such a vaccine if no alternative were reasonably available.[83]

Once the first vaccines were approved for emergency use by the FDA in late 2020 and early 2021, the controversy took a new turn: whether it is ethical for individuals to receive vaccines produced using adenoviruses that were produced in immortalized cell, such as those by Johnson & Johnson and Astra Zeneca, as opposed to vaccines produced using mRNA technology, such as those by Moderna and Pfizer, that only used immortalized cell lines for confirmation studies.[84] Among the more influential contributions to the discussion is a March 2021 statement issued by a group of American Catholic pro-life scholars in the fields of biomedical science, law, philosophy, and theology. The scholars emphasized that the cell lines currently in use do not contain the remains of any human fetus, and thus that there is “no real distinction” in moral terms between the vaccines respectively using immortal cell lines and mRNA in production.[85]

The statement’s irenic appraisal of the COVID vaccines ought to be helpful in negotiating the current debate, even if there is not full agreement regarding its conclusions. Furthermore, its approach, focusing on the specific nature of the immortalized cell lines, emphasizes the importance of approaching all questions regarding FTR (and for that matter, all ethical questions regarding biomedical research) with a firm grasp of both scientific facts and ethical principles. In short, due to the very remote connection between current vaccine production and abortion(s) performed long ago, such research is clearly distinguishable from the ongoing use of newly-obtained fetal tissue from contemporaneous elective abortions. The editors and authors of this Special Report have endeavored to contribute to the rigorous and multi-disciplinary approach that supports this conclusion, with hope that it will engage the interest of the increasing number of people concerned about the impact of biomedical science on the dignity and value of the human person.

POSTSCRIPT: The Impact of Dobbs v. Jackson Women’s Health Organization

The Supreme Court’s June 2022 decision in Dobbs v. Jackson Women’s Health Organization,[86] reversing Roe v. Wade[87] and returning regulation of procured abortion to the states, could significantly impact the “fetal-tissue economy” described in the foregoing article. The extent of such impact, however, will depend on a number of factors. First, for the foreseeable future, abortion will remain widely available, even past the point of fetal viability, in several of the largest states. Those states presumably will also allow a full extent of fetal tissue research and may, consistent with recent and ongoing efforts to liberalize their own laws on abortion, provide funding and other support for FTR.[88] Second, laws in other states that restrict abortion will not necessarily affect FTR—unless those states also have enacted specific restrictions on FTR, as 17 states have done.[89] Third, the changing legal landscape on abortion will likely accelerate the trend toward so-called “medical abortions,” the most common type being the combination of oral mifepristone and oral misoprostol. This will reduce the total amount of fetal tissue potentially available for donation and research. However, at least for the time being, a significant number of abortions, including all those performed after the first trimester, will continue to be performed in clinic or hospital settings where such donation can be facilitated.

The impact of Dobbs over the long term, of course, remains to be seen. Beyond its legal and constitutional rulings, Roe v. Wade and its progeny promoted a cultural norm in which abortion was seen as the primary option in response to unplanned and crisis pregnancies. The undoing of Roe as a legal norm is but the first step in revisiting cultural and social attitudes founded on the expectation of extremely permissive (by comparative international standards) access to abortion. Those attitudes color not only the personal and social response to “problem pregnancies” but norms regarding relations between the sexes, formation of families, expectations for career and employment, and, as the articles in this issue describe, the ethics of biomedical research. The future of FTR will be bound up in society’s reappraisal of the negative attitudes toward the protection of nascent human life fomented by Roe, specifically whether those attitudes be confirmed, or rejected and set aside.

 

References


[1] The Week Staff, “How Fetal Tissue Is Used in Medical Research,” The Week, October 24, 2015, https://theweek.com/articles/584576/how-fetal-tissue-used-medical-research.

[2] This essay will focus on HFT obtained as the result of induced abortion. The terms “fetus” and “fetal” are employed regardless of the gestational age at which the abortion is performed. The essay does not address, however, the closely related ethical issue of human embryo research, i.e., in vitro research conducted on embryos created for that purpose, or made available through the creation of excess embryos through in vitro fertilization.

[3] Select Investigative Panel of the House Energy and Commerce Committee, Final Report (U.S. House of Representatives: December 30, 2016). The Report has since been removed from the website of the Energy and Commerce Committee, and is available at: https://lifelegaldefensefoundation.org/wp-content/uploads/2020/01/Select_Investigative_Panel_Final_Report.pdf (Hereafter House Select Panel Report).

[4] R. Alta Charo, “Fetal Tissue Fallout,” New England Journal of Medicine 373, no. 25 (2015): 890–91, https://doi.org/10.1056/nejmp1510279; Sharmila Devi, “Anti-Abortion Groups Target Funding of Planned Parenthood,” The Lancet 386, no. 9997 (2015): 941, https://doi.org/10.1016/s0140-6736(15)00113-0; Dave Levitan, “Unspinning the Planned Parenthood Video,” July 21, 2015, FactCheck.org, https://www.factcheck.org/2015/07/unspinning-the-planned-parenthood-video/.

[5] Maria Dinzeo, “Jury Finds Abortion Foes Harmed Planned Parenthood, Awards Over $2 Million,” Courthouse News Service, November 15, 2019, https://www.courthousenews.com/jury-finds-abortion-foes-harmed-planned-parenthood-awards-870k/. The jury’s verdict has been appealed.

[6] The Times Editorial Staff, “Editorial,” Los Angeles Times, March 30, 2017, https://www.latimes.com/opinion/editorials/la-ed-planned-parenthood-charges-20170330-story.html.

[7] Sarah Kliff, “I Watched 12 Hours of the Planned Parenthood Sting Videos. Here’s What I Learned,” Vox, September 9, 2015, https://www.vox.com/2015/8/13/9140849/planned-parenthood-videos-unedited.

[8] Review of the Guidance on the Research Use of Fetuses and Fetal Material (Polkinghorne Report) (London: Her Majesty's Stationery Office, 1989), Cmnd. 762, paragraph 3 (emphasis supplied).

[9] Tetsuya Ishii and Koji Eto, “Fetal Stem Cell Transplantation: Past, Present, and Future,” World Journal of Stem Cells 6, no. 4 (2014): 404–20, http://dx.doi.org/10.4252/wjsc.v6.i4.404.

[10] Erling Norrby and Stanley B. Prusiner, “Polio and Nobel Prizes: Looking Back 50 Years,” Annals of Neurology 61, no. 5 (2007): 385–95, https://doi.org/10.1002/ana.21153.

[11] Kyle Christopher McKenna, “Use of Aborted Fetal Tissue in Vaccines and Medical Research Obscures the Value of All Human Life,” The Linacre Quarterly 85, no. 1 (2018): 13–17, https://doi.org/10.1177/0024363918761715.

[12] Gerard J. Boer, “Ethical Guidelines for the Use of Human Embryonic or Fetal Tissue for Experimental and Clinical Neurotransplantation and Research,” Journal of Neurology 242, no. 1 (1994): 1, 10, https://doi.org/10.1007/bf00920568.

[13] Boer, “Ethical Guidelines for the Use of Human Embryonic or Fetal Tissue,” 1, 10; Ishii & Eto, “Fetal Stem Cell Transplantation,” 409.

[14] Steven P. Wainwright et al., “Ethical Boundary-Work in the Embryonic Stem Cell Laboratory,” Sociology of Health & Illness 28, no. 6 (2006): 732–48, https://doi.org/10.1111/j.1467-9566.2006.00539.x.

[15] Wainwright et al., “Ethical Boundary-Work,” 742–44.

[16] Wainwright et al., “Ethical Boundary-Work,” 743.

[17] Consultants to the Advisory Committee to the Director, National Institutes of Health, Report of the Human Fetal Tissue Transplantation Research Panel (NIH: December 1988), https://repository.library.georgetown.edu/bitstream/handle/10822/821920/Fetal%20Tissue%20Panel%20Volume%201.pdf?sequence=1&isAllowed=y (hereafter Report of the Human Fetal Tissue Transplantation Research Panel).

[18] Report of the Human Fetal Tissue Transplantation Research Panel, 6.

[19] Report of the Human Fetal Tissue Transplantation Research Panel, 4.

[20] Report of the Human Fetal Tissue Transplantation Research Panel, 2.

[21] Report of the Human Fetal Tissue Transplantation Research Panel, 33–35.

[22] Report of the Human Fetal Tissue Transplantation Research Panel, 31–32.

[23] Report of the Human Fetal Tissue Transplantation Research Panel, 36.

[24] Noah V. Gimbel, “Fetal Tissue Research & Abortion: Conscription, Commodification, and the Future of Choice,” Harvard Journal of Law & Gender 40 (2017): 229, 236, https://harvardjlg.com/wp-content/uploads/sites/19/2012/01/jlg-winter-4.pdf.

[25] As the dissenters noted, the majority’s claim to sequester these issues amounted to an implicit endorsement of the morality of abortion, a judgment heavily reliant on the legality of abortion under Roe v. Wade. While the majority professed to acknowledge that the morality and legality are distinct issues, the repeated citation of Roe v. Wade—in particular by the panel’s chair, Judge Adams (a professed opponent of abortion and Roe)—clearly suffused its judgment that elective abortion should be considered a legitimate source of HFT for research.

[26] Report of the Human Fetal Tissue Transplantation Research Panel, 10.

[27] Report of the Human Fetal Tissue Transplantation Research Panel, 31.

[28] Report of the Human Fetal Tissue Transplantation Research Panel, 32.

[29] See McKenna, “Use of Aborted Fetal Tissue,” 16–17.

[30] James Burtchaell and James Bopp, “Dissenting Statement,” in Report of the Human Fetal Tissue Transplantation Research Panel (NIH: December, 1988), 47, 68.

[31] Burtchaell and Bopp, “Dissenting Statement,” 32, n. 13.

[32] Boer, “Ethical Guidelines for the Use of Human Embryonic or Fetal Tissue.”

[33] Boer, “Ethical Guidelines for the Use of Human Embryonic or Fetal Tissue,” 7.

[34] Naomi Pfeffer, “How Work Reconfigures an ‘Unwanted’ Pregnancy into ‘the Right Tool for the Job’ in Stem Cell Research,” Sociology of Health & Illness 31, no. 1 (2009): 98, 101–2; Julie Kent, “The Fetal Tissue Economy: From the Abortion Clinic to the Stem Cell Laboratory,” Social Science & Medicine 67, no. 11 (2008): 1747, 1749, https://doi.org/10.1016/j.socscimed.2008.09.027.

[35] Naomi Pfeffer, “What Has Happened to the Review of the Polkinghorne Guidelines on Research Using Fetal Tissue?” BioNews, April 20, 2009, https://www.bionews.org.uk/page_91690.

[36] John Keown, “The Polkinghorne Report on Fetal Research: Nice Recommendations, Shame about the Reasoning,” Journal of Medical Ethics 19 (1993): 114–20, https://doi.org/10.1136/jme.19.2.114.

[37] National Institutes of Health Revitalization Act of 1993, Pub. L. No. 103–43, Tit. I, Subtitle A, Part II, §§ 111-14, codified at 42 U.S.C. §§ 289g-1, 289-g2.

[38] The moratorium of NIH funding of FTR imposed in 1988 had been through the presidency of George H.W. Bush.

[39] 42 U.S.C. §§ 289g-1(b)(1), (2)(A) (emphasis supplied).

[40] 42 U.S.C. § 289g-2(a). The law also prohibits the designation of donated HFT to a particular recipient, the payment by the recipient of the cost of the abortion, and the use of HFT from a pregnancy deliberately initiated to provide HFT.

[41] 42 U.S.C. § 289g-2(e).

[42] V. Noah Gimbel, “Fetal Tissue Research & Abortion: Conscription, Commodification, and the Future of Choice,” Harvard Journal of Law & Gender 40, no. 1 (2017): 229, 236, https://harvardjlg.com/wp-content/uploads/sites/19/2012/01/jlg-winter-4.pdf.

[43] 45 C.F.R. §§ 46, 116.

[44] 45 C.F.R. Parts 160, 164 §§ A, E.

[45] Ohio, Indiana, Oklahoma, North Dakota, and South Dakota. See National Conference of State Legislatures, “Embryonic and Fetal Research Laws,” ncsl.org, January 1, 2016, https://www.ncsl.org/research/health/embryonic-and-fetal-research-laws/fb_source/message.aspx; Guttmacher Institute, “State Laws on Fetal Tissue Donation and Research,” Guttmacher.org, 2016, https://www.guttmacher.org/sites/default/files/infographic_attachment/fetaltissuemap.pdf.

[46] House Select Panel Report.

[47] House Select Panel Report, xix, 136ff.

[48] House Select Panel Report, 30.

[49] House Select Panel Report, 362–63.

[50] House Select Panel Report, 365–72. The dissenters to the 1988 NIH Fetal Tissue Research Panel Report predicted the nature of this “symbiotic relationship” between the abortion industry, fetal tissue procurers, and transplant researchers. Report of the Human Fetal Tissue Transplantation Research Panel, 53.

[51] House Select Panel Report, 365–72. See also 165–68, 186–97, 220–22 (describing embedded relationships in general).

[52] House Select Panel Report, 242–48.

[53] House Select Panel Report, 255–56.

[54] House Select Panel Report, 386.

[55] House Select Panel Report, 379.

[56] House Select Panel Report, 380–82.

[57] Kelly Puente, “OCDA Obtains $7.8 Million Settlement against Two Orange County Companies Accused of Selling Fetal Tissue for Profit,” Orange County Register, December 8, 2017, https://www.ocregister.com/2017/12/08/ocda-obtains-7-8-million-settlement-against-two-orange-county-companies-accused-of-selling-fetal-tissue-for-profit/.

[58] Jennifer Haberkorn, “Human Tissue Firm Cuts Ties with Planned Parenthood,” Politico, August 15, 2015, https://www.politico.com/story/2015/08/planned-parenthood-fetal-tissue-company-cuts-ties-videos-121371. The website of StemExpress does not currently list fetal tissue. “Homepage,” StemExpress, accessed November 17, 2021, https://www.stemexpress.com.

[59] HHS, “Statement of the Department of Health and Human Services,” HHS.gov, September 24, 2018, https://www.hhs.gov/about/news/2018/09/24/statement-from-the-department-of-health-and-human-services.html.

[60] Jessica Firger, “Planned Parenthood Will No Longer Accept Reimbursements for Fetal Tissue Donation,” Newsweek, October 13, 2015, https://www.newsweek.com/planned-parenthood-will-no-longer-accept-reimbursements-fetal-tissue-donation-382748.

[61] House Select Panel Report, 30.

[62] House Select Panel Report, 374–88 (responding to researchers and institutions); 388–96 (responding to Panel Minority).

[63] Ishii & Eto, “Fetal Stem Cell Transplantation,” 404–5.

[64] House Select Panel Report, 401.

[65] House Select Panel Report, 375.

[66] House Select Panel Report, 375.

[67] House Select Panel Report, 377.

[68] Norrby and Prusiner, “Polio and Nobel Prizes,” 388.

[69] Norrby and Prusiner, “Polio and Nobel Prizes,” 388; John F. Enders, Thomas H. Weller, and Frederick C. Robbins, “Cultivation of the Lansing Strain of Poliomyelitis Virus in Cultures of Various Human Embryonic Tissues,” Science 109, no. 2822 (1949): 85–87, https://doi.org/10.1126/science.109.2822.85.

[70] House Select Panel Report, 381–83.

[71] Megan Scudellari, “How iPS Cells Changed the World,” Nature 534 (2016), 310–12, https://doi.org/10.1038/534310a.

[72] Ishii & Ito, “Fetal Stem Cell Transplantation,” 408.

[73] Gina Kolata, “Parkinson’s Research Is Set Back by Failure of Fetal Cell Implants,” The New York Times, March 8, 2001, http://www.nytimes.com/2001/03/08/us/parkinson-s-research-is-set-back-by-failure-of-fetal-cell-implants.html.

[74] Alison Abbott, “Fetal-Cell Revival for Parkinson’s,” Nature 510 (2014): 195, https://www.nature.com/polopoly_fs/1.15387!/menu/main/topColumns/topLeftColumn/pdf/510195a.pdf.

[75] Ishii & Eto, “Fetal Stem Cell Transplantation,” 409.

[76] Olle Lindvall, “Clinical Application of Neuronal Grafts in Parkinson’s Disease,” Journal of Neurology 242, Supplement 1 (1994): S54–56, https://doi.org/10.1007/bf00939243.

[77] “Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research,” Notice Number: NOT-OD-19-128, NIH.gov, July 26, 2019, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-128.html.

[78] “Update on Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research,” Notice Number: NOT-OD-21-111, NIH.gov, April 16, 2021, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-111.html.

[79] “HHS Removes an Administrative Requirement for Human Fetal Tissue Research Proposals,” NIAID Funding News, May 5, 2021, https://www.niaid.nih.gov/grants-contracts/hft-research-policy-change.

[80] Katelyn Burns, “Coronavirus Treatment Research Is Being Held Up by Trump’s Ban on the Use of Fetal Tissue,” Vox, March 19, 2020, https://www.vox.com/policy-and-politics/2020/3/19/21186743/coronavirus-treatment-research-delay-trump-fetal-tissue-ban. See also Christopher O. Tollefson, “It’s Unethical to Use Fetal Tissue in COVID-19 Research,” Public Discourse, April 22, 2020, https://www.thepublicdiscourse.com/2020/04/62734/.

[81] Kylie Su Mei Yong et al., “Humanized Mice as Unique Tools for Human-Specific Studies,” Archivum Immunologiae et Therapiae Experimentalis 66 (2018): 245, 261, https://doi.org/10.1007/s00005-018-0506-x.

[82] Teodor-D Brumeanu et al., “A Human-Immune-System (HIS) Humanized Mouse Model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2ryc KO. NOD) for COVID-19, bioRxiv, January 29, 2021, https://doi.org/10.1101/2020.08.19.251249.

[83] Helen Watt, “COVID-19 Vaccines and Use of Foetal Cell-Lines,” Anscombe Bioethics Center, April 27, 2020, http://www.bioethics.org.uk/images/user/covidbriefing2.pdf. See also Nicanor Pier Giorgio Austracio, “Using Morally Controversial Human Cell Lines after Dignitatis personae,” National Catholic Bioethics Quarterly 10, no. 2 (2010): 265–72, https://doi.org/10.5840/ncbq201010252; McKenna, “Use of Aborted Fetal Tissue,” 14.

[84] This Special Report includes essays by Lee and Feeney, Prentice, and Grant addressing this question from scientific and religious perspectives.

[85] “Statement from Pro-Life Catholic Scholars on the Moral Acceptability of Receiving COVID-19 Vaccines,” Ethics & Public Policy Center, March 5, 2021, https://eppc.org/news/statement-from-pro-life-catholic-scholars-on-the-moral-acceptability-of-receiving-covid-19-vaccines/.

[86] Dobbs v. Jackson Women’s Health Organization, 597 U.S. --; 142 S. Ct. 2228 (2022).

[87] Roe v. Wade, 410 U.S. 113 (1973).

[88] Disputes over funding of FTR can extend to overall appropriations for public colleges and universities. See, for example, “Pitt Gets State Funds Despite Fetal Tissue Research Dispute,” AP News, July 7, 2022, https://apnews.com/article/pittsburgh-university-of-government-and-politics-bc49e535b8883888702b1bf528f97abe. The dispute was resolved when provisions to restrict funding of FTR at the University of Pittsburgh were segregated from the general appropriation for Pitt and other Commonwealth institutions.

[89] Tara Sander Lee et al., “Human Fetal Tissue from Elective Abortions in Research and Medicine: Science, Ethics, and the Law,” Issues in Law and Medicine 35, no. 1 (2020): 3–61.