Regulation of Human Fetal Tissue Research in the United States

The decision by the Trump administration in 2019 to restrict federal funding for human fetal tissue research (FTR) followed the pattern set by previous presidential administrations of promoting or restricting funding of such research. Regulation of research using human fetal tissue (HFT) from induced abortion at the federal level in the United States has been via funding, in particular funding provided by the National Institutes of Health (NIH). The general regulatory scheme is sometimes phrased as “what is not prohibited is allowed”; i.e., unless there is a specific statutory prohibition, any type of research is legal. Discretionary funding, rather than legal prohibition, is then the leverage to promote different research priorities.

Before proceeding, it is necessary to distinguish the subject of this discussion—fetal tissue—from cell lines derived from fetal tissue and from embryonic stem cells. Fetal tissue implies organs or body parts freshly obtained from an induced abortion or miscarriage (i.e., primary tissue), and continued research with fetal tissue requires an ongoing supply of freshly obtained tissue. Cell lines are derived from primary tissue by growing individual cells in laboratory culture dishes, and once established, a cell line can be propagated in the laboratory for years, decades, or in some cases indefinitely; there is no need to obtain fresh tissue or continually re-initiate the cell line. The currently used fetal cell lines were established using tissue from singular induced abortions that occurred in the 1960s, 1970s and 1980s, and the cells have grown in the lab ever since. For context, note that the first human cell line—HeLa—was derived from a biopsy of cervical carcinoma tissue in 1951, and this cell line continues to be grown in labs and used in experiments. But research with HeLa cells is definitively not cervical carcinoma tissue research, just as research with abortion-derived cell lines such as WI-38 cells or HEK293 cells is not FTR. Conflating fetal tissue with cell lines deceptively misrepresents the science. Thus, the claim that the polio vaccine was produced using fetal tissue is an unscientific falsehood. Likewise, embryonic stem cells are not fetal tissue; they are derived by culturing cells obtained by the destruction of very young human embryos (less than 7 days old) and proliferate as cell lines in the laboratory.[1] In the United States, research and vaccine production with abortion-derived cell lines is not specifically regulated, while embryonic stem cell research is federally funded and subject to different regulations than those used regarding human FTR.

In March 1988, President Reagan’s Department of Health and Human Services (HHS) placed a moratorium on funding for all research using fetal tissue from induced abortion; this moratorium continued through the administration of President George H. W. Bush. Soon after taking office, President Clinton on January 22, 1993, signed a memorandum lifting the Reagan moratorium, allowing federal funding of human FTR to resume. Subsequently, Congressman Henry Waxman led an effort that resulted in passage of legislation in 1993 allowing federal funding of human FTR for transplantation. The statute (42 U.S.C. § 289g-1 and § 289g-2) specifically addressed fetal tissue transplant research funded by the Secretary of HHS: “The Secretary may conduct or support research on the transplantation of human fetal tissue for therapeutic purposes.”[2] However, the statute is silent on basic research using fetal tissue. As discussed above, funding for basic research has been allowed at the discretion of the NIH Director and the HHS Secretary.

Both the Clinton Memorandum and the Waxman statute were predicated on funding potentially therapeutic transplants of fetal tissue into patients, and as part of the 1993 statute, NIH is required to make an annual report to Congress of all funded transplantation research. Two large controlled clinical trials were funded to transplant fetal brain tissue from induced abortions into Parkinson’s patients; the results, published in 2001 and 2003, showed that the fetal tissue transplants did not improve patients’ conditions and in a number of cases actually worsened their condition.[3] Subsequently, NIH reports to Congress stated that it has not provided any funding for transplantation research with HFT since FY2003. Nevertheless, basic research using HFT has continued to be funded by NIH, most recently at $106 million in FY2019 and an estimated $116 million to be spent in FY2020.[4]

The 1993 federal statute has remained relatively unchanged since its initial passage, and various reviews and reports for Congress have not added substantively to the debate in a way that has resulted in modifications. The undercover videos released by the Center for Medical Progress in 2015, exposing problems in enforcement of the statute as well as ethical violations, led to investigations by both the U.S. House and Senate in 2016, culminating in referrals to the Department of Justice. Yet despite several proposals for reforms in the federal FTR statute, none of the proposed pieces of legislation were enacted.

State governments have moved ahead while Congressional action has been stalled, passing laws regarding human FTR as well as respectful disposition of the bodies of fetuses. The relevant federal statute regarding fetal tissue, 42 U.S.C. § 289g-1(e), specifically allows for the conduct of fetal tissue transplantation only in accordance with applicable state and local law. At least 17 states have enacted policies that limit research and experimentation on fetal tissue from induced abortion or that restrict any monetary transactions regarding HFT use or transfer.[5]

At the federal level, executive actions have continued to bring changes in federal policy on human FTR. After news revelations about multimillion-dollar federal contracts from NIH-funded research using fetal tissue from abortions, HHS in the fall of 2018 initiated an audit of federally funded FTR. In addition, NIH announced in December 2018 that it would invest up to $20 million over the next two years to develop alternatives to FTR.[6] Finally, on June 5, 2019, HHS issued a decision to restrict federal funding of FTR.[7] The restrictions covered multiple points:

·     Discontinue all intramural research (research within NIH) that uses fetal tissue from induced abortion.

·     Allow a multimillion-dollar contract with University of California, San Francisco (UCSF) that uses fetal tissue to expire with no extension of funding.

·     Allow extramural grants and contracts (research conducted outside NIH, e.g., at universities) to finish already funded projects, but all proposals for new funding or renewal of funding will receive additional review by an Ethics Advisory Board that will recommend whether, in light of the ethical considerations, the research should be funded.

·     Renewal of commitment to develop and accelerate alternative models and techniques that do not use fetal tissue.

NIH and HHS subsequently issued notices implementing these changes in expectations for grant and contract proposals[8] and clarifying grant application instructions,[9] effective with any applications on or after September 25, 2019. As explained earlier, the notices make clear distinctions between what is covered by additional review—primary fetal organs, tissues, and cells obtained from elective abortion—versus already established human fetal cell lines, human embryonic stem cells, or cells and tissues that were not derived from an elective abortion.

The new HHS policy gives ethical consideration primacy in funding decisions regarding FTR. This is especially evident in the convening of the Human Fetal Tissue Research Ethics Advisory Board. According to statute 42 U.S.C. § 289a-1(b), the Secretary of HHS cannot withhold funds from an approved NIH project because of ethical considerations unless an Ethics Advisory Board has been convened, reviews the project for ethical considerations, and advises the Secretary regarding project funding.[10] This option for ethics review was placed into statute in 1993, but this is the first time any administration or HHS Secretary has invoked the Ethics Board. The statute spells out the procedures and makeup of the Ethics Board and specifies that “the term ‘ethical considerations’ means considerations as to whether the nature of the research involved is such that it is unethical to conduct or support the research.”[11] The ethics of the research are the sole purview of this board as the science is reviewed separately by other review panels.[12]

A preliminary announcement on December 23, 2019 heralded that nominations for the Ethics Board would be requested in 2020,[13] with the formal call for nominations published in the Federal Register on February 20, 2020.[14] As specified in statute, the Ethics Board was to be composed of 15 individuals, with at least one-third but no more than one-half as scientists, and at least one ethicist, at least one physician, at least one attorney, and at least one theologian. Their charge was to “advise, consult with, and make recommendations to, the Secretary of Health and Human Services (Secretary) regarding the ethics of research involving human fetal tissue (HFT) proposed in NIH grant and cooperative agreement applications and R&D contract proposals.”[15] A Federal Register announcement gave notice of a meeting of the Human Fetal Tissue Research Ethics Advisory Board scheduled on July 31, 2020.[16]

On July 31, 2020, the Human Fetal Tissue Research Ethics Advisory Board convened its first meeting with a session open to the public that included a welcome and charge to the Board members, brief introductions of the 15 highly credentialed professionals selected by the HHS Secretary for service, explanations of confidentiality and meeting procedures, and comments from the public.[17] The Board then went into closed session for over 5 hours to discuss grant and contract proposals. The closed session was to allow full discussion of proposal details while maintaining confidentiality of personal and proprietary information in the proposals, in line with NIH standard procedures for other proposal review committees.[18] For each proposal, after extensive discussion of the ethics of the research and justifications required in proposal submission, a vote was taken on whether to recommend to the Secretary that funding be withheld or not withheld. Of the fourteen proposals considered, the Ethics Advisory Board voted to withhold funds for thirteen of the research proposals, and to not withhold funds for one of the proposals. As required by statute, the Ethics Advisory Board submitted a report to the Secretary of HHS, the Committee on Energy and Commerce of the U.S. House of Representatives, and the Committee on Health, Education, Labor and Pensions of the U.S. Senate. This public report provides further insight into the deliberations of the Ethics Advisory Board while maintaining confidentiality regarding discussions and proposal details.[19] Interestingly, despite some (including two members of the Board) who complained that the Board was “stacked” against human FTR, the report belies that assertion, showing a broad range of votes based on serious consideration of the proposals. Over one-third of the votes were unanimous (0-15) or nearly unanimous (1-14) for withholding funds, thus including even those members of the Board who strongly supported FTR.

The policy decisions of the Trump Administration, the outcome of this 2020 Ethics Advisory Board meeting, and the recommendations of the Ethics Advisory Board regarding funding for proposed research using fetal tissue from induced abortion set a direction for the future of all FTR funding, a direction poised to switch the science to more modern and less controversial methods and biological materials. An analysis subsequent to the Ethics Advisory Board meeting showed that there was still substantial extramural funding from NIH going to FTR at 68 different academic organizations throughout the United States; the analysis pointed out “significant inadequacies in the way NIH categorizes and reports human fetal tissue research,” and recommended a number of changes in NIH policy.[20] However, as noted at the outset of this article, each presidential administration can alter the direction of FTR, and this is what happened following the 2020 election and the swearing in of President Biden in January 2021.

Only Congress can pass changes in the statutes themselves, but the executive branch can make new rules and regulations that embroider specific details on the statutes. The outgoing Trump Administration in early January 2021 published proposed new rules for FTR in the Federal Register;[21] the proposed changes would have tightened restrictions on federal funding for FTR, strengthened safeguards and program integrity requirements, and stopped abuses and failings of the FTR regulations.[22] But, after taking comments, the Biden HHS quietly dropped the proposed new regulations and the new regulations did not go into effect.

On April 16, 2021, with little notice, the Biden Administration abruptly discarded all of the restrictions on FTR funding.[23] This included cancelling any further ethical reviews of extramural grant proposals by the Ethics Advisory Board and disbanding the Board; HHS Secretary Becerra said he had determined that there were “no new ethical issues that require special review.” [24] NIH issued a revised notice regarding extramural research that “HHS/NIH will not convene another NIH Human Fetal Tissue Research Ethics Advisory Board.”[25] Intramural research was also quietly resumed via an internal e-mail at NIH. Despite a letter from 137 Members of Congress urging reinstatement of the Ethics Advisory Board and ethical review of FTR proposals,[26] HHS and NIH are moving ahead rapidly to restore funding and reactivate many FTR projects. It remains to be seen whether total FTR funding will be increased, whether funding for alternatives to fetal tissue will continue or be cut, and whether any steps will be taken to address ethical abuses that were identified by the Ethics Advisory Board.

References

[1] For more details, see 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, https://issuesinlawandmedicine.com/product-category/spring-2020/; David A. Prentice, “Exploring Alternatives to Fetal Tissue Research,” Invited Scientific Testimony, Joint Hearing of the Subcommittee on Healthcare, Benefits, and Administrative Rules and Subcommittee on Government Operations, House Oversight & Government Reform Committee, U.S. House of Representatives, December 13, 2018, https://s27589.pcdn.co/wp-content/uploads/2019/01/Prentice-Testimony-HCBAR-GO-Fetal-Tissue-12.13.18.pdf; David A. Prentice, “Adult Stem Cells: Successful Standard for Regenerative Medicine,” Circulation Research 124, no. 6 (2019): 837–39, https://doi.org/10.1161/CIRCRESAHA.118.313664; Junying Yu and James A. Thomson, “Embryonic Stem Cells,” in Regenerative Medicine 2006 (NIH, 2006), https://embryology.med.unsw.edu.au/embryology/images/4/4d/NIH_Regenerative_Medicine_2006.pdf.

[2] Research on Transplantation of Fetal Tissue, 42 U.S.C. § 289g-1, https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section289g-1&num=0&edition=prelim; Prohibitions Regarding Human Fetal Tissue, 42 U.S.C. §289g-2, https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section289g-2&num=0&edition=prelim.

[3] See details within Sander Lee et al., “Human Fetal Tissue from Elective Abortions in Research and Medicine;” Prentice, “Exploring Alternatives to Fetal Tissue Research.”

[4] “Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC),” NIH, February 24, 2020, http://report.nih.gov/categorical_spending.aspx.

[5] See list in Sander Lee et al., “Human Fetal Tissue from Elective Abortions in Research and Medicine.”

[6] “Notice of Intent to Publish Funding Opportunity Announcements for Research to Develop, Demonstrate, and Validate Experimental Human Tissue Models That Do Not Rely on Human Fetal Tissue,” Notice Number: NOT-OD-19-042, NIH.gov, December 10, 2018, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-042.html.

[7] HHS, “Statement from the Department of Health and Human Services,” HHS.gov, June 5, 2019, https://www.hhs.gov/about/news/2019/06/05/statement-from-the-department-of-health-and-human-services.html.

[8] “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.

[9] “Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research,” Notice Number: NOT-OD-19-137, NIH.gov, August 23, 2019, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-137.html.

[10] Certain Provisions Regarding Review and Approval of Proposals for Research, (b) Ethical Review of Research, 42 U.S.C. § 289a-1, https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section289a-1&num=0&edition=prelim.

[11] “Ethical Considerations” Defined, 42 U.S.C. § 289a-1(b)(6), https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section289a-1&num=0&edition=prelim.

[12] Review as Precondition to Research, 42 U.S.C. § 289a-1(a), https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title42-section289a-1&num=0&edition=prelim.

[13] “Notification of HHS Plan to Publish a Statement Announcing the Intention to Convene an NIH Human Fetal Tissue Research Ethics Advisory Board for Fiscal Year 2020 and Soliciting Nominations,” Notice Number: NOT-OD-20-053, NIH.gov, December 23, 2019, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-053.html.

[14] HHS Notice of Committee Establishment, Notice of Intent To Convene, and Call for Nominations for the NIH Human Fetal Tissue Research Ethics Advisory Board for Fiscal Year 2020, 85 Fed. Reg. 9785 (February 20, 2020), https://www.federalregister.gov/documents/2020/02/20/2020-03302/hhs-notice-of-committee-establishment-notice-of-intent-to-convene-and-call-for-nominations-for-the.

[15] Secretary of HHS, “NIH Human Fetal Tissue Research Ethics Advisory Board—FY2020 Charter, NIH.gov, March 6, 2020, 1, https://osp.od.nih.gov/wp-content/uploads/84589-HHS-2020-Charter-362020.pdf.

[16] Notice of Meeting; NIH Human Fetal Tissue Research Ethics Advisory Board-FY2020, 85 Fed. Reg. 42889 (July 15, 2020), https://www.federalregister.gov/documents/2020/07/15/2020-15241/notice-of-meeting-nih-human-fetal-tissue-research-ethics-advisory-board-fy2020.

[17] See Agenda, Charter, and other information at NIH, “Archives of the NIH Fetal Tissue Research Ethics Advisory Board—FY2020,” NIH.gov, accessed October 22, 2021, https://osp.od.nih.gov/biotechnology/nih-human-fetal-tissue-research-ethics-advisory-board/.

[18] See, e.g., “Integrity and Confidentiality in NIH Peer Review,” NIH, June 18, 2015, https://grants.nih.gov/policy/research_integrity/confidentiality_peer_review.htm.

[19] “Report of the Human Fetal Tissue Research Ethics Advisory Board—FY2020,” NIH, accessed October 22, 2021, https://osp.od.nih.gov/wp-content/uploads/HFT_EAB_FY2020_Report_08182020.pdf.

[20] Tara Sander Lee and James L. Sherley, “A Policy and Funding Evaluation of Human Fetal Tissue Research,” On Science 2 (2020): https://lozierinstitute.org/a-policy-and-funding-evaluation-of-human-fetal-tissue-research/.

[21] Establishment of Safeguards and Program Integrity Requirements for Health and Human Services-Funded Extramural Research Involving Human Fetal Tissue, Notice of Proposed Rulemaking, 86 Fed. Reg. 2615 (January 13, 2021), https://www.federalregister.gov/documents/2021/01/13/2020-29107/establishment-of-safeguards-and-program-integrity-requirements-for-health-and-human-services-funded.

[22] David Prentice and Tara Sander Lee, “Comment on Proposed Rule Establishing Safeguards and Program Integrity Requirements for HHS-Funded Human Fetal Tissue Research,” Charlotte Lozier Institute, February 12, 2021, https://s27589.pcdn.co/wp-content/uploads/2021/04/Comment-HHS-Proposed-Rule-Fetal-Tissue-Regulations-Charlotte-Lozier-Institute.pdf.

[23] Kelly Servick, “Biden Administration Scraps Human Fetal Tissue Research Restrictions,” Science, April 16, 2021, https://www.sciencemag.org/news/2021/04/biden-administration-scraps-human-fetal-tissue-research-restrictions.

[24] Marilynn Marchionne, “Federal Officials Reverse Limits on Fetal Tissue Research,” ABC News, April 16, 2021, https://abcnews.go.com/Health/wireStory/federal-officials-reverse-limits-fetal-tissue-research-77124933Federal.

[25] 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.

[26] Houston Keene, “HHS Should Reinstate Fetal Tissue Research Ethics Board, 37 Senators and 100 Reps Demand in Letter,” Fox News, June 23, 2021, https://www.foxnews.com/politics/hhs-becerra-fetal-tissue-research; Letter from Sen. Wicker et al. to HHS Secretary Xavier Becerra, June 23, 2021; https://www.wicker.senate.gov/public/_cache/files/df63d995-e1b6-4d54-ac22-4e61299b87e2/final-fetal-tissue-letter.pdf.