MORATORIA AND INNOVATION IN THE REPRODUCTIVE SCIENCES: OF PRETEXT, PERMANENCE, TRANSPARENCY, AND TIME-LIMITS.
As progress in the biosciences soldiers forth, new breakthroughs can often be swept up in a common narrative, that is, the narrative of science as a disruptive threat. Responding to perceived threats, policymakers the world over have frequently overreacted to these developments by enacting shortsighted legislation. These knee-jerk reactions often entail a ban or pause on the science to be explored, thereby foregoing a dialog or term-limited oversight. In this paper, we explore the history and transparency of such moratoria.
In the United States, moratoria come in the form of one of the following four mechanisms: first, enacted permanent statutes; second, enacted renewable riders--amendments "extraneous to the main purpose of the bill to which it is attached" (1)--typically annual appropriations bills; third, executive orders and executive policies issued by the president or other Executive branch officials; and fourth, regulations promulgated by governmental agencies or commissions at either the state or federal level.
The repeal of a moratorium has everything to do with the mechanism by which it was established. The repeal of statutory bans or riders require a majority of votes in the House of Representatives, sixty votes in the Senate (to withstand a legislative filibuster, and the ability to survive a veto (if deployed)); by contrast, an executive order or a regulation can be--and many have been--superseded by successive administrations.
The target of a moratorium is often born of its origin: a statute can ban scientific experimentation in both the private and public sectors, or a rider can ban the expenditure of federal funds dedicated to that field of research. Moratoria can criminalize a science as easily as it could bar only the expenditure of federal funds on such pursuits, with some qualifications (related to constitutional law).
Conversely, executive orders typically only bear on federal agencies of the Executive Branch. However, if FDA approval is required for a specific scientific pursuit, an executive order can affect both public- and private-sector researchers by way of existing statutes requiring FDA approval before promotion of a drug or device.
Calls for moratoria have targeted varied areas of science ranging from genetically modified foods (2) to certain plant life (3)--and at both the state and federal level. The federal government has effectuated a few such bans, such as the Obama Administration's decision to restrict federal funds for gain-of-function experiments on potentially harmful viruses. (4)
One area in which moratoria have played a starring role in scientific development is reproductive research, which is frequently opposed by politicized religious ideologies. Table 1 summarizes the bans proposed and enacted in the reproductive sphere at both the federal level and local levels. For the latter category, the Table specifies the method by which the federal government executed the moratorium.
Behind these moratoria, an important question looms large: are the legislative and executive branches of government seeking to pause a given research until such time that society can answer important moral and scientific questions about its consequences, what we deem a "pause," or is the government trying to bar a given research outright in light of already-considered scientific and ethical ramifications, termed a "ban"?
The problem, however, is when a "ban" masquerades as a "pause," when moratoria are enacted and justified to discuss these important considerations when, in reality, it was enacted to effectively bar the science regardless of the discussions. We refer to this phenomenon as a "pretextual ban." This lack of transparency is what we aim to ferret out. Yes, such categorizations are imprecise at best, though there are a few indicia that inform our thinking.
In some rare cases the wolf comes not in sheep's clothing, but dressed as a wolf; Congress may be explicit in its justification of certain bans. For example, Congress may push for a pause specifically citing uncertainty in a science's consequences, as a pause would allow the scientific and ethical communities--as well as the body politic--to evaluate the ramifications of the science in question before forging ahead. (16) On the other hand, outright bans--or attempts to enact them--explicitly sometimes cite perceived immoral implications of a given science as motivating its permanent prohibition.
Intent can also be divined or inferred from myriad sources. Consider the longevity of a ban; if a moratorium continues many years, it is unlikely that lawmakers are awaiting clarification on a disputed scientific or moral question: rather such discussions have likely taken place and lawmakers have made a decision--either a decision to maintain the ban or a decision that moving to upend the ban is not worth the political capital. On the other hand, if moratoria are brief, it is far more likely that they were enacted so as to afford the scientific and ethical communities the ability to have these discussions before moving ahead. Admittedly, this rule is not perfect--moratoria could be in place for years but regularly revisited to account for any ethical or scientific breakthroughs--but it is nevertheless a decent barometer.
So, where do the existing moratoria fall in this typology? We discuss five examples in what follows, but Table 2 provides a summary on this score.
HUMAN EMBRYO RESEARCH
The legislative concern surrounding human embryo research--pre-viability cells lacking cognizable humanoid structure, typically under six days old and numbering only approximately 100 per sample--began in 1975, following earlier ethical critiques of in vitro fertilization ("IVF") by biologist-ethicist Leon Kass and theologian Paul Ramsey and subsequent call for IVF and embryo transfer bans. (17) The moratorium was limited to prohibiting the expenditure of federal funds on such research. (18) After several years of deliberating the ethics of such research, which involved the Congressionally-mandated Ethics Advisory Board ("EAB") holding hearings in eleven cities over five months, the EAB concluded in 1979 that such research was ethically permissible if certain conditions were met:
In all, several thousand hearing notices were sent to professional organizations, public interest groups, universities, clergy, and individuals. Everyone who requested to appear was heard; 179 individuals presented testimony in hearings in Bethesda (Maryland), Boston, Seattle, San Francisco, Atlanta, Kansas City, Detroit, Philadelphia, Denver, Dallas and New York City.... In addition, the Board received over 2000 letters and postcards, some of which were forwarded from President Carter and Secretary Califano. (19)
But in 1980, the EAB was dissolved. As part of a political reorganization to reduce the size of the government under Ronald Reagan, the EAB's funds were transferred to the newly-formed President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research ("President's Commission") with the "understanding that the role of ethics advising would also be transferred." (20) While the President's Commission indeed advised on more macro questions such as "Defining Death," (21) it did not adjudicate specific research requests like the EAB had, including the morality of human embryo research. Thus, EAB approval requirement remained but the Board's approval was impossible to receive, creating a de facto moratorium.
Several unsuccessful attempts to resuscitate the EAB were mounted throughout the 1980s and early 1990s--the National Institutes of Health ("NIH") Directors under Presidents Reagan and Bush lobbied their respective Administrations to reconstitute the EAB. (22) When the NIH Revitalization Act of 1992 passed both legislative houses, it included a provision to nullify the requirement of EAB approval. President George Herbert Walker Bush vetoed the Act for unrelated reasons, (23) which meant that the EAB remained defunct. The following year, however, Congress again passed the bill and President Clinton signed it, thereby lifting the moratorium.
In response to lifting the ban, the NIH formed the Embryo Research Panel ("the Panel") to discuss the ethical issues involved in such research before it would approve research applications. "The Panel's five meetings were open to the public, and it heard public testimony from forty-six individuals and organizations." (24) With specific conditions--including valid research designs, lack of available alternatives, minimizing the number of embryos and the embryo's development at the time of experimentation, informed consent, compensation limited to cover costs, IRB oversight, and equitable selection of donors to distribute benefits and risks--the Panel concluded that the NIH should be able to fund research on embryos generally, and that, when embryos could not be secured via the byproducts of IVF, the NIH should be free to fund research that created embryos solely for the purpose of research.
President Clinton refused to implement the Panel's second conclusion. Thus, he "directed [the] NIH not allocate any resources for such research." (25) Recognizing Clinton's openness to the lion's share of the changes, Congress introduced and passed the Dickey-Wicker amendment, "the response of the Republican-controlled House and Senate to ethical concerns surrounding federal funding for any research involving human embryos." (26)
The moratorium--first an outright activity ban, then a subsequent funding moratorium--on human embryo research is both permanent and transparent. Though the moratorium was at first arguably the work of bureaucratic ineptitude, (27) politics was solely to blame for subsequent failures to jumpstart this research. Moral approval from a panel on the ethics of such research was first granted nearly four decades ago and it has been subsequently reaffirmed, though the diversity (or lack thereof) of the panelists' viewpoints (or lack thereof) has been the subject of scrutiny or criticism. Rather blatant politics have defined this moratorium. At the very least, government actors were above board about their motivations.
HUMAN FETAL TISSUE TRANSPLANTATION RESEARCH FROM INDUCED ABORTIONS
The story of the moratorium on human fetal research, or cells derived from early-stage fetuses that already have a recognizable humanoid structure, offers a stark comparison. In 1974, the National Research Act created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and charged it with "conduct[ing] an investigation and study of the nature and extent of research involving living fetuses, the purposes for which such research has been undertaken, and alternative means for achieving such purposes." (28) Until the Commission offered recommendations, federal funds were barred from being expended on such research. (29) When the Commission published its report the following year, Research on the Fetus, (30) it concluded that therapeutic and non-therapeutic research was acceptable on both a fetus and a pregnant woman, given sufficient safety protocols and oversight.
Starting in 1975, the Department of Health, Education, and Welfare ("HEW") (the precursor to today's Department of Health and Human Services) issued regulations (31) that largely "substantially adopt[ed] the Commission's recommendations." (32)
All research directed toward fetuses and pregnant women is first subjected to general limitations: (1) the necessary completion of appropriate animal studies; (2) minimal risk to the fetus in nontherapeutic research; (3) separation of researchers from decisions regarding the timing or method of abortion or regarding the viability of the fetus ex utero; (4) no introduction of significant changes into the abortion procedure solely in the interests of research where such changes may cause greater than minimal risk to either the fetus or the pregnant woman; and (5) no inducements offered to abort for purposes of research. (33)
There were even more regulations depending on whether the research was aimed at the fetus or the pregnant mother. Research on a pregnant mother was always permissible so long as the mother's consent was obtained. (34) Research on the nonviable fetus ex utero, or a living but nonviable fetus, simply required that "[n]o procedural changes which may cause greater than minimal risk to the fetus or the pregnant woman will be introduced into the procedure for terminating the pregnancy solely in the interest of the activity." (35)
Research on a fetus in utero was another question. Such experimentation required consent of both the mother and father, and it required the risk to the fetus be "minimal." Without a definition, this framework may have been theoretically sound but vulnerable to misapplication or overbroad interpretation, i.e. classifying everything as too risky. (36)
The EAB was permitted to issue a waiver for increasingly risky procedures, but, again, the EAB was discontinued without having issued a single waiver. And even when a majority of an ad hoc advisory group that reported to the Director's Advisory Committee (37) supported lifting the ban, HHS Secretary Louis Sullivan overruled the report's conclusion. When Congress attempted to legislatively override the moratorium, President George H.W. Bush vetoed it: his veto statement read, "I believe this moratorium is important in order to prevent taxpayer funds from being used for research that many Americans find morally repugnant and because of its potential for promoting and legitimatizing abortion." (38)
The moratorium was lifted in 1993 via President Bill Clinton's policy memorandum, in which he noted that the ban was thought to be "temporary," but "[c]ontrary to the recommendations of a National Institutes of Health advisory panel" the year after the moratorium was enacted, it was extended "indefinitely." (39) "Five years later," Clinton then remarked, "the evidence is overwhelming.... We must let medicine and science proceed unencumbered by anti-abortion politics." (40) Shortly thereafter, Clinton signed the NIH Revitalization Act of 1993 into law, which paved the way for such research to be federally funded.
Through the summer of 2017, "Republicans in the House of Representatives have launched an effort to prevent the U.S. National Institutes of Health from funding research using fetal tissue obtained from elective abortions." (41) The draft language bars federal funding if "used to conduct or support research using human fetal tissue if such tissue is obtained pursuant to an induced abortion." (42) As reported by Science, "[t]he language mirrors a recommendation made earlier this year by Republicans on a now disbanded special House panel--the Select Investigative Committee on Infant Lives," (43) which held hearings in the wake of undercover videos released purporting to portray Planned Parenthood clinics mishandling fetal tissue. (44) What's more, the push at the federal level mirrors measures from state legislators barring such research. (45)
Given the ban's duration as well as explicit statements made by political leaders concerning its enactment and withdrawal, it is all but certain that the moratorium represented an ideological ban. But, again, government actors were transparent in both furthering and dissolving the ban.
HUMAN-NONHUMAN CHIMEWRA RESEARCH
The moratorium on human-nonhuman chimera research, or animal embryos into which human cells are injected to produce certain human organs for medical therapy, falls squarely into the "pause" category--at least thus far. In September 2015, the NIH "abruptly announced it was suspending funding for studies that introduce human stem cells into animal embryos." (46) The NIH's announcement included its reasoning:
Given the rapid expansion of potential research models employed beyond the scope described above, NIH would like to undertake a deliberative process to evaluate the state of the science in this area, the ethical issues that should be considered, and the relevant animal welfare concerns associated with these types of studies (47)
The statement did not indicate how long the NIH intended to keep the ban in place.
Two months later, the NIH held the Workshop on Research with Animals Containing Human Cells to assess the relevant issues. (48) Among the panelists leading these discussions were physicians, ethicists, lawyers, scientists, and veterinarians. (49) The Workshop's conclusion can be gleaned from the NIH's subsequent proposal to lift the ban: while there are significant challenges to creating chimeric models, there is clear interest and potential in producing animal models with human tissues or organs for studying human development, disease pathology, and eventually organ transplantation. (50)
The NIH thus proposed reinstating the research's funding while adding a new steering committee to oversee such research beyond the normal review process, which is to consider: the specifics of both the human and animal cells; "the likely effects on the animal"; "planned monitoring (including animal welfare assessments);" and "any staging of proposed research (e.g., assessing the outcome of a particular experiment before conducting a further experiment)." (51)
Lifting the funding ban after just fifteen months was not originally planned. But if repealed, this is a paradigmatic "pause": as concerns mounted over the science's ethics and safety, the regulatory process paused its progress to take stock and reevaluate, ultimately enacting further reviews but letting the science proceed with caution.
A rider attached to the 2016 federal appropriation bill barred the FDA from considering--and thus approving--research "in which a human embryo is intentionally created or modified to include a heritable genetic modification." (52) It was extended the following year. (53) This particular ban's recency makes it slightly more difficult to discern Congress's thinking, but the statements and reports made by congresspersons as well as the greater scientific context offer helpful insight. Congress first took notice in 2015, "sparked by the announcement in April [of that year] that researchers in China had edited the genomes of human embryos." (54)
When the rider was first proposed, the July 2015 House Report accompanying the rider explicated the ban's introduction:
Editing of the human germ line may involve serious and unquantifiable safety and ethical issues. Federal and non-Federal organizations such as the National Academy of Sciences and National Academy of Medicine will soon engage in more extensive scientific analysis of the potential risks of genome editing and a broader public discussion of the societal and ethical implications of this technique. (55)
The Chairman of the House Subcommittee on Research and Technology, Lamar Smith (R--TX), echoed these concerns, stating that such experiments were "alarming," claiming that "most of the scientific community members have been clear: the science and ethics of this new technology must be resolved in order to prevent dangerous abuses and unintended consequences." (56) More, the Chairman referenced an Op-Ed in Science that "recommended a moratorium on further research, while creating public forums for scientists, ethicists and policy makers to discuss 'the attendant ethical, social, and legal implications of genome modification.'" (57) These statements indeed demonstrate a desire to pause research to flesh-out the ethical foundation and consequences.
Reports and discussions in the scientific community confirm this intuition. "[T]he National Academy of Sciences and the National Academy of Medicine convened the Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations" (58) to study the "scientific underpinnings as well as the clinical, ethical, legal, and social implications of the use of human genome editing technologies in biomedical research and medicine." (59) Such reports evince a genuine desire to hold off on research on heritable germline research so that these conversations could take place before the science progresses beyond where we as a nation are comfortable.
On the other hand, two factors may suggest that it is actually a pretextual ban, using a pause as a pretense to ban the practice altogether. First, the rider is far from narrowly tailored, encompassing other scientific procedures that were not the focus of the committee's wariness. A prime example of this is securing "savior siblings," or embryos that are a sufficiently close tissue match such that their cord blood can be used to "cure" their sibling of a disease, such as anemia. "[W]hen in vitro fertilization fails to secure tissue-matched embryos for intrauterine transfer," (60) genome editing is required to make the sibling a human leukocyte antigen match, but such work would be prohibited by this language. Second, appropriation riders "such as the Dickey-Wicker Amendment have displayed remarkable longevity across several administrations and variable congressional constellations." (61) The appropriation rider banning germline modification was renewed for the new fiscal year without discussion, again suggesting it may share Dickey-Wicker's fate. Ultimately, though, these two data points do not outweigh contrary evidence.
Therefore, the ban appears to be a pause for further discovery and discussion, though there exists a fear that these discussions will never occur, and the pause becomes pretext for a permanent ban.
MITOCHONDRIAL REPLACEMENT THERAPY
The very same appropriations bill that bars the FDA from considering germline gene editing also precludes executing mitochondrial replacement therapy ("MRT"), a set of techniques aimed at allowing carriers of mitochondrial disease to reproduce by replacing one woman's mitochondria from the egg of another. In the above-mentioned House Report, the only reference to mitochondrial replacement techniques was a note stating, "that the EDA commissioned a consensus study from the Institute of Medicine ("IOM") on 'Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases.'" (62)
On February 3, 2016, the IOM published its report, which exhaustively detailed the new scientific facets of the technology as well as expounded on each potential ethical pitfall. Overall, "the committee conclude[d] that it is ethically permissible to conduct clinical investigations of MRU' under some circumstances. (63) In particular, the committee prescribed multiple conditions that had to be met--such as transferring male embryos only, FDA oversight, adherence to prior ethical standards relating to embryo research, and delineated study protocols--for the practice to be ethical.
A study published in June 2016 in Nature found that by using a new protocol, fewer than two percent of potentially fatal mutant mitochondrial DNA remained. (64) In December, though, another Nature study found that that number was actually as high as fifteen percent of cases. (65) But while these numbers were borne out in a petri dish, the risk to humans is far less certain: for example, potentially fatal mutant mitochondrial DNA have not been found in non-human primates subjected to MRT. (66)
Since the IOM published its study, there have been no further congressional hearings or reports on mitochondrial replacement therapy. (There have only been cursory references to mitochondrial diseases writ large.) MRT remains barred in the United States. American doctors have even controversially traveled abroad to perform the procedure, (67) though the FDA has contacted at least one of the physicians to warn against further marketing or performing these procedures against FDA regulations. (68)
Without similar legislative history denoting explicit ethical concerns over MRT-the science was not named explicitly in either the Subcommittee Report or at the hearing--the subsequent IOM recommendation, and the delay, it's uncertain whether the moratorium began as a pause for further exploration or an ideological ban. Regardless, it is likely more appropriately classified today as a pretextual ban given the noticeable lack of discussion and conversation on the topic despite the IOM's conclusions.
Our tripartite government was designed "to ensure due deliberation and inquiry," thereby safeguarding the assent of the people. (69) Such a system offers a viable analogue for scientific research. If a moratorium is imposed when a scientific field sits on the precipice of an ethically uncertain discovery, pausing research offers all relevant stakeholders the opportunity to temporarily reevaluate the science's underpinnings and implications. If sound, progress; if otherwise, consider more permanent halts. And as shown, these moratoriums can--and have--come in multiple forms.
These potholes along the road of progress can indeed serve the science in question by ensuring both that the people are behind it and that its critics are given an opportunity to be heard. Pauses for the sake of deliberation do just that. And when critics populate the majority, there is reason to ban the science altogether, until such a time as its proponents regain popular opinion. The problem, as we have identified, is when lawmakers who disagree with the science pause its progress in the guise of deliberation but lack follow through once scientific or moral questions have been answered contrary to their ideology. If such a ban is indeed put forward--or extended-for ideological reasons contrary to the conclusion of scientists and ethicists alike, lawmakers must be upfront about their thinking such that the voters can weigh in on the ideological costs and benefits of a science's ban, both by contacting their elected officials and, ultimately, by their votes. Otherwise, we risk sidestepping democratic accountability and simultaneously forego untold treasures of scientific discovery.
Russell A. Spivak, J.D.*
Glenn Cohen, J.D. ([dagger])
Eli Y. Adashi, M.D., M.S. ([double dagger])
* Russell A. Spivak, J.D., is an associate at Wilmer Cuder Pickering Hale and Dorr, LLP and a 2017 graduate of the Harvard Law School in Cambridge, MA. Russell received his B.S. from the Massachusetts Institute of Technology. Mr. Spivak may be reached at email@example.com.
([dagger]) I. Glenn Cohen, J.D., is a Professor of Law at Harvard Law School, the Co-Director of the Petrie-Flom Center for Health Law Policy, Biotechnology, and Bioethics at Harvard University, a Hastings Center Fellow, and an Editor-in-Chief of the Journal of Law and the Biosciences. Prof. Cohen received Hs B.A. with Honors from the University of Toronto and his J.D., magna cum laude from Harvard Law School.
([double dagger]) Eli Y. Adashi, M.D., M.S., is a Professor of Medical Science and former Dean of The Warren Alpert Medical School at Brown University. Dr. Adashi received his M.D. from the Sackler School of Medicine, completed an Obstetrics and Gynecology residency at Tufts University, and pursued a fellowship in Reproductive Endocrinology and postdoctoral training in reproductive biology at Johns Hopkins University and at the University of California at San Diego, respectively. Dr. Adashi earned an M.S. from Harvard in Health Care Management and was given a Doctor Honoris Causa from the Poznan University of Medical Sciences. Dr. Adashi is a member of The Hastings Center's Advisory Council, Board of Governors of Tel Aviv University, and chair of the Medical Executive Committee and the Medical Advisory Council of the Jones Foundation for Reproductive Medicine.
(1) Eli Y. Adashi & Glenn Cohen, The FDA is Prohibited From Going Germline, 353 science 545 (2016) (referring to rider of Consolidation Appropriation Act of 2016). This rider foreclosed the possibility of a human germline modification process for the year of 2017 and may possibly extend through 2018 depending on the decision of the annual renewal. Id.
(2) See CONSTANCE A. JOHNSON, LIBRARY OF CONGRESS, RESTRICTIONS ON GENETICALLY MODIFIED ORGANISMS 1,210 (Mar. 2014), https://www.loc.gov/law/help/restrictions-on-gmos/restrictions-on-gmos.pdf (listing scientific organizations asserting GMOs have no additional safety concerns compared to non-GMOs).
(3) See Angus Chen, Kratom Drug Ban May Cripple Promising Painkiller Research, SCI. AM. (Sep. 27, 2016), https:// www.scientificamerican.com/article/kratom-dmg-ban-may-cripple-promisingpainkiller-research/ (discussing DEA's plan to place kratom on most restricted list of controlled substances). Kratom is a plant that acts on opioid receptors in the brain and is being researched as a potential medication for reducing morphine dependence given its non-addictive properties in mice. Id.
(4) See Sara Reardon, US Suspends Risky Disease Research, 514 NATURE 411 (Oct. 23, 2014), http://www.nature.com/news/us-suspends-risky-disease-research-l. 16192 (predicting temporary funding ban may become long-term depending on advisory board's decision). In this case, the gain-of-function experiments involve vaccines for preventing influenza, severe acute respiratory syndrome, and Middle East Respiratory syndrome. Id.
(5) VETERANS HEALTH ADMIN., DEPT. OF VETERANS AFFAIRS, REQUIREMENTS FOR THE PROTECTION OF HUMAN SUBJECTS IN RESEARCH, VHA HANDBOOK 1200.05(2), at 21 (2014) (establishing regulations for how Veteran services may be employed).
(6) See generally Channah Jarrell, No Worldwide Consensus: The United Nations Declaration on Human Cloning, 35 GA. J. INT'L & COMP. L. 205, 206-8 (2006) (discussing global reactions to human cloning).
(7) See Embryonic and Fetal Research Laws, NAT'L CONF. OF STATE LEGISLATURES (Jan. 1, 2016), http://www.ncsl.org/research/health/embryonic-and-fetal-research4aws.aspx (analyzing various ways states regulate stem cell research).
(8) See Varnee Murugan, Embryonic Stem Cell Research: Decade of Debate from Bush to Obama, 82 YALE J. BIOLOGY & MED. 101,101 (2009), available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744932/#sltitle (describing the impact President Bush's policies had on stem cell research).
(9) See David Stout, In First Veto, Bush Blocks Stem Cell Bill, N.Y. TIMES (July 19, 2006), http://www.nytimes.com/ 2006/07/19/washington/19cnd-stem.html (explaining President Bush's stance on Stem Cell Research).
(10) Aroob Khokhar, Barack Obama Executive Order 13505, November 2008, THE EMBRYO ENCYCLOPEDIA PROJECT (June 17, 2010), https://embryo.asu.edu/pages/barack-obama executive-order-13505-november-2008 (reviewing the issuance of President Obama's Executive Order 13505).
(11) See Fritz H. Bach & Harvey V. Fineberg, Callfor Moratorium on Xenotransplants, 391 NATURE 326 (1998) (highlighting the need to carefully review the science behind xenotransplants).
(12) See Tim Dean, Xenotransplantation Ban IJfied in Australia, AUSTRALIAN LIFE SCIENCE (Oct. 12, 2009), https://web.archive.Org/web/20091215005407/http://www.lifescientist.com.au/article/329402 /xenotransplantation_ban_lifted_australia (articulating the medical reasoning behind lifting the xenotransplants ban in Australia).
(13) See Food & Drug Administration, U.S. Dep't of Health & Human Services, Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans: Guidance for Industry, food & Drug Admin., https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatory Information/Guidances/X enotransplantation/UCM533036.pdf (last updated Dec. 2016) (providing guidance to sponsors and applicants of xenotransplantation products).
(14) See Food & Drug Administration, U.S. Dep't of Health & Human Services, PHS Guideline on Infectious Disease Issues in Xenotransplantation, food & drug admin. (Jan. 19, 2001), https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInfo rmation/Guidances/Xenotransplantation/UCM092858.pdf (explaining the risks encompassed by xenotransplantation as it may invoke infectious disease).
(15) See Adashi & Cohen, supra note 1, at 545 (citing Consolidated Appropriations Act, 2016, Pub. L. No. 114-113, 129 Stat. 2242 (2015), www.congress.gov/bill/114th-congress/housebill/2029/text) (restricting how the FDA uses its funds).
(16) See Adashi & Cohen, supra note 1, at 546 nn.9-10 (explaining that scientific uncertainty posed by novel technology impedes Congress to move forward with legislation).
(17) See Dep't of Health, Ed., & Welfare, HEW Support of Research Involving Human In Vitro Fertilisation and Embryo Transfer, ETHICS ADVISORY BOARD 11-14 (1979), https://archive.Org/stream/hewsupportofresellunit#page/nl/mode/2up (describing the research and published articles that brought attention to the concern of IVF).
(18) See Margaret O'Brien Steinfels, In Vitro Fertilisation: Ethically Acceptable' Research, 9 HASTINGS CTR. REP. 5, 5 (1979), http://onlineHbrary.wiley.com/doi/10.2307/3560785/pdf (describing the limitations placed on IVF).
(19) See Dep't of Health, Ed., & Welfare, supra note 17, at 81 (discussing the responses received by the Ethics Advisory Board in response to the hearings).
(20) See J. BENJAMIN HURLBUT, EXPERIMENTS IN DEMOCRACY: HUM. EMBRYO RES. AND THE POL. OF BIOETHICS, 77-78 (2017) (describing the end of the EAB and the transition to the President's Commission).
(21) President's Comm. for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, Defining Death: A Report on the Medical, Legal and Ethical Issues in the Determination of Death (July 1981), available at https://scholarworks.iupui.edu/bitstream/handle/1805/707/Definining%20death%20%201981.pdf?sequence=l&isAllowed=y.
(22) See George H. W. Bush, Message to the House of Representatives Returning Without Approval the National Institutes of Health Revitalization Amendments of 1992, in 1 PUBLIC PAPERS OF THE PRESIDENTS OF THE UNITED STATES, GEORGE BUSH 1992-1993 (1992).
(23) Id. (arguing the amendments are unacceptable on ethical, fiscal, administrative, legal, and philosophical grounds).
(24) Jennifer C. Fletcher, US Public Policy on Embryo Research: Two Steps Forward, One Large Step Back, 10 HUMAN REPROD. 1875,1875 (1995).
(25) See Fletcher, supra note 23, at 1876.
(26) See Press Release, The White House, Statement By the President (Dec. 2, 1994), https://clintonwhitehouse6.archives.gov/1994/12/1994-12-02-president-on-nih-and-human-embryo-research.html (discussing the decision to remove federal funding for human embryo research). See also Eliot Marshall, Clinton Rules Out Some Studies, 266 SCIENCE 1634,1634-1635 (1994) (providing details regarding President Clinton's limitation on the N1H to discontinue federal funding toward human embryo research); Warren E. Leary, Clinton Rules Out Federal Money for Research on Human Embryos Created for That Purpose, N.Y. times, (Dec. 3, 1994), http://www.nytimes.com/1994/12/03/us/clinton-rules-federal-money-for-research-human-embryos-created-for-that -purpose.html (discussing President Clinton's decision to remove funding from human embryo research but to leave the option open for future research on unused embryos at fertilization clinics).
(27) See Megan Kearl, Dickey-Wicker Amendment, 1996, THE EMBRYO PROJECT ENCYCLOPEDIA, https://embryo.asu.edu/pages/dickey-wicker-amendment-1996 (last accessed Mar. 14, 2018) (discussing the congressional reasoning for passing this amendment to eliminate federal funding on human embryos).
(28) See HURLBUTT, supra note 21, at 77 (discussing the debates surrounding embryonic research providing arguments supporting the purposes behind the research).
(29) National Research Service Award Act of 1974, Pub. L. No. 93-348, [section] 201, 88 Stat. 342, 348 (1974) (amending "protection[s] of human subjects involved in biomedical and behavioral research and for other purposes").
(30) Id. [section] 213. Until recommendations were made by the Commission "the Secretary [could] not conduct or support research in the United States or abroad on a living human fetus, before or after the induced abortion of such fetus, unless such research [was] done for the purpose of assuring the survival of such fetus." Id.
(31) NAT'L COMM. FOR THE PROTECTION OF HUMAN SUBJECTS OF BIOMEDICAL & BEHAVIORAL RESEARCH, RESEARCH ON THE FETUS: REPORT AND RECOMMENDATIONS (1975). "The charge to the Commission [was] to investigate and study research involving the living fetus and to make recommendations to the Secretary, DHEW, on 'policies defining the circumstances (if any) under which such research may be conducted or supported.'" Id. at 61. "[T]herapeutic research directed toward the health care of the pregnant woman or the fetus raises little concern, provided it meets the essential requirements for research involving the fetus, and is conducted under appropriate medical and legal safeguards." Id. at 72.
(32) 45 C.F.R. [section][section] 46.201-211 (1975) (describing the conditions for conducting research on pregnant women, fetuses, and neonates).
(33) Kathleen Markey, Federal Regulation of Fetal Research: Toward a Public Policy Founded on Ethical Reasoning, 31 U. Miami L. Rev. 675, 687 (1977), https://repository.law.miami.edu/cgi/viewcontent.cgi?referer=&httpsredir=l&article=2575&co ntext=umlr (discussing regulations for all research by the Department of Health, Education, and Welfare).
(34) See id. at 689 (citing 45 C.F.R. [section] 46.206 (1976)) (suggesting research on the mother is the "preeminent right").
(35) See id. at 691 n.95, 692 (quoting 45 C.F.R. [section] 46.206 (1976)) (discussing the preliminary conditions that allow or bar such research).
(36) 45 C.F.R. [section] 46.206(a)(4) (1975) (stating that no procedure causing more than minimal risk can be performed).
(37) See Markey, supra note 33, at 689 (discussing one stance on fetal research). See also CONFERENCE COMMITTEE ON FETAL RESEARCH AND APPLICATIONS, FETAL RESEARCH AND APPLICATIONS: A CONFERENCE SUMMARY (1994) (explaining current state of fetal research). "In the case of a fetus, almost all interventions exceed minimal risk[.]". Id at 8.
(38) See REPORT OF THE ADVISORY COMMITTEE TO THE DIRECTOR, NAT'L INST, OF HEALTH, HUMAN FETAL TISSUE TRANSPLANTATION RESEARCH (Dec. 14, 1988) (summarizing findings of NIH Transplant Research Panel).
(39) See H.R. Doc. No. 102-349 (1992) (explaining reasoning for executive veto of H.R. 2507).
(40) See William Clinton, Remarks on Signing Memorandums on Medical Research and Reproductive Health and an Exchange With Reporters, THE AMERICAN PRESIDENCY PROJECT (Jan. 22, 1993), http://www.presidency.ucsb.edu/ws/index.php?pid=46219 (commenting on reasoning for suggestion made to Shalala). See also William Clinton, Memorandum on Fetal Tissue Transplant Research, THE AMERICAN PRESIDENCY PROJECT (Jan. 22, 1993), http://www.presidency.ucsb.edu/ws/index.php?pid=46289 (giving order to lift moratorium on fetal research).
(41) Meredith Wadman, House Republicans Move to Bar Funding for NIH Fetal Tissue Research, SCIENCE MAGAZINE, http://www.sciencemag.org/news/2017/07/house-republicans-move-bar-funding-nih-fetal-tissue-research (last visited Mar. 14, 2018) (citing H.R. 115, 115th Cong, (as reported by Staff of Subcomm. on Lab., Health and Human Servs., Educ., and Related Agencies of the H.R. Comm. on Appropriations 2017)).
(42) Departments of Labor, Health and Human Services, and Education, and Related Agencies Appropriations Act, H.R. 3358 [section] 528 (2018).
(43) Wadman, supra note 41.
(44) Id. See House Creates Select Panel to Investigate Handling of Infant Lives, ENERGY COM (Oct. 7, 2015), https://energycommerce.house.gov/news/press-release/house-creates-select-panelinvestigate-handling-infant-lives.
(45) See, e.g., Charles Lain Fehman, Indiana University, State Government Clash Over Aborted Fetail Tissue Research, WASH. FREE BEACON (Aug. 23, 2017, 3:18 PM), http://freebeacon.com/issues/indianauniversity-state-government -clash-aborted-fetal-tissue-research/. In August 2017, Indiana University research scientists asked a federal court to invalidate a 2016 state law criminalizing research conducted with the tissue of aborted fetuses, alleging that the law poses unconstitutional restraints on interstate commerce and academic freedom. Id. See also Alison Thoet, In Texas, Legal Battle Over Abortion Law Hangs Over Special legislative Session, PBS: NEWSHOUR (July 24, 2017, 4:47 PM), http://www.pbs.org/newshour/updates/texas-legal-batde-abortion-law-hangs-speciallegislative-session/ (discussing The Center for Reproductive Rights' challenge to a state law requiring abortion providers to cremate or bury aborted embryonic or fetal tissue); Gary Robbins, UCSD Caught in Debate Over Fetal Tissue Research, SAN DIEGO UNION-TRIBUNE (Mar. 24, 2016, 7:14 PM), http://www.sandiegouniontribune.com/news/science/sdut-ucsd-fetaltissue-research-2016mar24-story.html (discussing a special House committee's request for information of individuals working with human fetal tissue); David Wahlberg, Fetal Tissue Ban Could Impact Medical Research in Wisconsin, WISCONSIN STATE J. (Aug. 9, 2015), http://host.madison.com/wsj/news/local/health_med_fit/fetal-tissue-ban-could-impact-medical-research-in -wisconsin/artideJ2d70666-3650-548f-9638-4b9eb420a220.html. Researchers are worried that a Wisconsin bill banning the use of aborted fetal tissue in experiments could criminalize important medical research. See Wahlberg, supra. About one hundred labs on campus use fetal tissue cells in studies on cancer, heart disease, and other conditions. Id. The bill's lead sponsor, Rep. Andre Jacque, believes the bill is establishing a "higher standard" and that researchers could still use fetal tissue from miscarriages in order to create new cell lines. Id.
(46) Jocelyn Kaiser, NIH Mom to Lift Moratorium on Animal-Human Chimera Research, SCIENCE MAGAZINE, http://www.sciencemag.org/news/2016/08/nih-moves-lift-moratorium-animal-human-chimera-research (last accessed Mar. 14, 2018). The sudden pause suspended future federal support for studies by researchers interested in creating pig-human or sheep-human chimeras in order to generate organs for transplantation. Id.
(47) Id. NIH's associate director for science policy Carrie Wolinetz stated her confidence that the proposed changes will enable the NIH research community to move forward in this area of science in a responsible manner and emphasized that the proposal is not a prohibition on chimera research. Id. For example, NIH current guidelines do not prohibit studies that add human stem cells to primate embryos up to and including the blastocyst stage, and the agency wants to tighten its existing stem cell guidelines to prohibit such studies. Id.
(48) See NAT'L INSTITUTES OF HEALTH, WORKSHOP ON RESEARCH WITH ANIMALS CONTAINING HUMAN CELLS: AGENDA (Nov. 6, 2015), available at https://osp.od.nih.gov//wpcontent/uploads/2015/11/Chimera_Agenda_Draft_11_03_15(public).pdf. Workshop topics included the introduction of human pluripotent cells into early-stage non-human vertebrate animal embryos, introducing human neural stem cells or progenitor cells into non-human vertebrate animal embryos or fetuses, and ensuring the responsible conduct of research with animals containing human cells. Id.
(49) See id.
(50) See id. See also NIH Research Involving Introduction of Human Pluripotent Cells into Non-Human Vertebrate Animal Pre-Castrulation Embryos, NAT'L INSTITUTES HEALTH (Sept. 23, 2015), https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-158.html (explaining the NIH's view on lifting the ban).
(51) Request for Public Comment on the Proposed Changes to the NIH Guidelines for Human Stem Cell Research and the Proposed Scope of an NIH Steering Committee's Consideration of Certain Human-Animal Chimera Research, 81 Fed. Reg. 51,921 (Aug. 5, 2016), https://www.federalregister.gov/documents/2016/08/05/2016-18601/request-for-public-comment-on-the-proposed-changes-to -the-nih-guidelines-for-human-stem-cell (explaining the Steering Committee's review process beyond the scope of the normal review process).
(52) Consolidated Appropriations Act of 2016, Pub. L. No. 114-92, [section] 749,129 Stat. 2242, 2283 (2015) (including barring FDA from considering research where human embryo is intentionally created or modified).
(53) Consolidated Appropriations Act, 2017, Pub. L. No. 115-31, [section] 736,131 Stat. 135, 173 (2017) (extending rider barring FDA from considering research where human embryo is intentionally created or modified).
(54) Sara Reardon, US Congress Moves to Block Human-Embryo Editing, NATURE (June 25, 2015), http://www.nature.com/news/us-congress-moves-to-block-human-embryo-editing-l. 17858 (reporting Congress's cognizance on embryo modification after Chinese research breakthrough editing human embryo genomes).
(55) H.R. REP. NO. 114-205, at 69 (2015), https://www.c0ngress.g0v/l 14/crpt/hrpt205/CRPT114hrpt205.pdf (explaining why regulation of human germ line is required).
(56) Press Release, Congressman Lamar Smith, Chairman, Comm. on Sci., Space, and Tech., The Science and Ethics of Genetically Engineered Human DNA (June 16, 2015), https://science.house.gov/sites/republicans.science.house.gov/files/documents/HHRG-114SY15-WState-S000583-20150616.pdf (addressing scientific community's concerns regarding science and ethics of human germ line research).
(57) See id. (discussing the need for more work and research before increasing patient treatments).
(58) David Baltimore et al., A Prudent Path Forwardfor Genomic Engineering and Germline Gene Modification, 348 SCIENCE 36, 37 (Apr. 3, 2015).
(59) See NAT'L ACAD, OF SCI., HUMAN GENOME EDITING: SCIENCE, ETHICS, AND GOVERNANCE 13 (2017) (discussing the ethical ramifications of genome editing).
(60) Cohen et al. The FDA Is Prohibitedfrom Going Germline, 353 SCIENCE 545, 546 (2016) (explaining which editing of genome of a human embryo is affected by the rider).
(61) See id. (citing Rodriguez et al., Am. J. bloeth. 20 (Mar. 2011)) (describing the seeming lack of action taken on finding alternatives for germline modification); On Human Gene Editing: International Summit Statement, INTERNATIONAL SUMMIT ON HUMAN GENE EDITING (Dec. 3, 2015), http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID= 12032015a. (describing the effects of scientific advances in molecular biology of the past 50 years).
(62) See H.R. REP. No. 114-205, supra note 55, at 65, (citing COMM. ON THE ETHICAL & SOCIAL POLICY CONSIDERATIONS OE NOVEL TECHNIQUES FOR PREVENTION OF MATERNAL TRANSMISSION OF MITOCHONDRIAL DNA DISEASES, MITOCHONDRIAL REPLACEMENT TECHNIQUES: ETHICAL, SOCIAL, AND POLICY CONSIDERATIONS (Enriquetta C. Bond & Ellen Wright Clayton eds, 2016) http://www.nap.edu/21871).
(63) COMM. ON THE ETHICAL & SOCIAL POLICY CONSIDERATIONS OF NOVEL TECHNIQUES FOR PREVENTION OF MATERNAL TRANSMISSION OF MITOCHONDRIAL DNA DISEASES, MITOCHONDRIAL REPLACEMENT TECHNIQUES: ETHICAL, SOCIAL, AND POLICY CONSIDERATIONS 9 (Enriquetta C. Bond & Ellen Wright Clayton eds., 2016) (explaining committee conclusions after ethical examination of MRT).
(64) See Louise A. Hyslop et al., Letter, Towards Clinical Application of Pronuclear Transfer to Prevent Mitochondrial DNA Disease, 545 NATURE 683, 683 (2016) (describing conflicting studies in determining potentially fatal amount of mutant mitochondrial DNA).
(65) Eunju Kang et al., Mitochondrial Replacement in Human Oogtes Carrying Pathogenic Mitochondrial DNA Mutations, 540 nature 270, 270-275 (2016).
(67) Jill Neimark, Unexpected Risks Found In Replacing DNA To Prevent Inherited Disorders, NAT'L PUBLIC RADIO (Jan. 1, 2017), http://www.npr.org/sections/health shots/2017/01/01/507244429/unexpected-risks-found-in-editing-genes-to-prevent-inheriteddisorders.
(68) Letter from Mary A. Malarkey, Director, Office of Compliance and Biologies Quality Center for Biologies Evaluation and Research, to Dr. John Zhang, Chief Executive Officer, Darwin Life, Inc. and New Hope Fertility Center (Aug. 4, 2017), available at https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatorylnfo rmation/ComplianceActivities/Enforcement/UntidedLetters/UCM570225.pdf. See also Susan Scutti, James Masters & Susannah Cullinane, FDA Warns '3-Parent' Baby Fertility Doctor Over Marketing, CNN (Aug. 7, 2017,10:49 A.M.), http://www.cnn.com/2017/08/07/health/fda-3parent-fertiBty-zhang/index.html.
(69) JOSEPH STORY, 2 Commentaries on the Constitution [section] 699 (1833).
Table 1. Science Federal Moratorium in Any Way? Y/N If Y, How? Recombinant DNA N N/A technology Human Embryo Y First, Executive Research Regulations: Dept. of Health, Education and Welfare regulations required approval from Ethics Advisory Board. Second, Funding Rider: The Dickey-Wicker Amendment Human Fetal Tissue Y Executive Policy: Transplantation Executive Policy to enact Research from a funding ban. A later Induced Abortions Executive Memorandum undid the ban. Reproductive N N/A cloning Human embryonic N N/A stem cell research Xeno-transplantation N N/A Human-Nonhuman Y Agency Regulation Chimera-Research Germline Y Funding Limitation via an Modification appropriations Rider Mitochondrial Y Funding Limitation via an Replacement appropriations rider Therapies (interpreted to include MRT) Scicnce Additional Notes Recombinant DNA Multiple U.S. municipalities technology (states, counties and townships) regulated it. Human Embryo President Clinton barred funding Research the creation human embryos solely for research in 1995. Human Fetal Tissue The VA currently bans it: Transplantation "research in which the focus Research from is either a fetus, or human fetal Induced Abortions tissue, in-utero or ex-utero (or uses human fetal tissue), cannot be conducted by VA [researchers] while on official duty, at VA facilities, or at VA-approved off-site facilities." (5) Reproductive Some states and countries cloning banned it. (6) (Some of the countries that did so did this legislatively, while others signed non-binding international agreements and failed to enact domestic legislation to give such agreements force.) Human embryonic Some states ban the practice stem cell research altogether, whereas others bar using state funds for such research. (7) In 2001, President Bush restricted the number of approved human embryonic stem cell lines. (8) In 2006, he used his first veto on a bill that would expand federally funded embryonic stem cell research. (9) President Obama signed an Executive Order in his first year to increase the number of approved human embryonic stem cell lines, but would not permit federal funding for Embryonic Stem cell lines from cloned embryos. (10) Xeno-transplantation Calls for it as early as 1998. (11) A ban was proposed in Europe, but failed. It was banned in Australia from 2004-2009. (12) The U.S. FDA has issued Industry Guidance on related clinical issues (13) and infectious disease risks. (14) Human-Nonhuman NIH sought public comment to lift Chimera-Research recently enacted, limited ban on Human-Nonhuman Animal Chimera Embryo on Aug. 5, 2016. Germline The FDA cannot expend funds to Modification review and accept IND applications. (15) Mitochondrial Replacement Therapies Table 2 Science Pause/Transparent Ban/Pretextual Ban Human Embryo Research Transparent Ban Human Fetal Tissue Transplantation Transparent Ban Research from Induced Abortions Human-Nonhuman Chimera Research Pause Germline Modification Pause (Likely, but too soon to tell) Mitochondrial Replacement Therapies Pretextual Ban
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|Title Annotation:||Eighth Annual Symposium; Black Market Gold: Medical and Transplant Tourism|
|Author:||Spivak, Russell A.; Cohen, Glenn; Adashi, Eli Y.|
|Publication:||Journal of Health & Biomedical Law|
|Date:||Mar 22, 2018|
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