GERM-LINE GENE EDITING AND CONGRESSIONAL REACTION IN CONTEXT: LEARNING FROM ALMOST 50 YEARS OF CONGRESSIONAL REACTIONS TO BIOMEDICAL BREAKTHROUGHS.

• Author: Spivak, Russell A.

1. INTRODUCTION 22 II. RECOMBINANT DNA (01/01/1969 - 12/31/1978) 23 III. IVF (01/01/1978 - 12/31/1982) 26 IV. CLONING (01/01/1994 - 12/31/1998) 30 V. STEM CELLS (06/01/1998 - 08/30/2015) 35 VI. CONCLUSION 37 VII. APPENDIX 39 Table 1: Bills Relating to Recombinant DNA 39 Table 2: Bills Relating to In Vitro Fertilization 41 Table 3: Bills Relating to Cloning 43 Table 4: Bills Relating to Stem Cells 44 I. INTRODUCTION

   On December 18, 2015, President Obama signed into law a policy rider forestalling the therapeutic modification of the human germ line by prohibiting the Food and Drug Administration (FDA) from considering such applications. (1) Triggered by the unprecedented discovery of novel genome-editing tools and their application to the human embryo, (2) this congressional reaction cut short the ongoing national conversation on the very acceptability of such interventions. These conversations included, most significantly, the National Academies-sponsored International Summit on Human Gene Editing and the Consensus Study of the National Academy of Medicine on the Scientific, Medical, and Ethical Considerations of Human Gene Editing. (3) The rider was then renewed the following year. (4) Perhaps more significantly, the statute in question also undermines current efforts of the FDA to adjudicate germ line-modifying technologies to prevent mitochondrial DNA diseases. (5) Thus far, what little analysis there has been of this rider it has focused on the present. In this essay we seek to provide the long view. The rider is but the latest example of Federal legislative and regulatory reaction to biomedical breakthroughs. By discussing the history of federal reaction to four other such breakthroughs (Recombinant DNA, IVF, Cloning, Stem Cells), a tale that lasts almost 50 years, we can better situate and understand the current debate and congressional action and better predict where we may go next. We exhaustively reviewed congressional reactions--Bills proposed, passed, or important public statements by members of Congress--and summarize that history in this essay.

2. RECOMBINANT DNA (01/01/1969 - 12/31/1978)

   While our story begins with Recombinant DNA, the national scientific landscape of the middle of the 20th century can be contextualized by calls for transparency. That only came in the form of the National Research Act of 1974, (6) which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. (7) The Act would not cover the genetic sciences of recombinant DNA, so when scientific pursuit thereof began in earnest, there were, unsurprisingly, calls for its governmental oversight. (8)

   The first successful production of recombinant DNA appeared in publications in 1972 and 1973 by multiple scientists across the United States. (9) In light of its potential applications, there were immediate calls for its governance and oversight. (10) The initial attempts to regulate recombinant DNA research did not take place at the federal level; rather, states and municipalities began debating whether they wanted to permit such research to continue in their borders. Maryland and New York passed statewide legislation governing research institutions in its borders, while California, Illinois, Massachusetts, New Jersey, and Wisconsin debated similar measures. (11) Berkeley, CA, Emeryville, CA, Amherst, MA, Cambridge, MA, Waltham, MA, and Princeton, NJ were the four municipalities to pass regulations that oversaw recombinant DNA activities via already existing or newly created local health boards or public officials. (12) Ann Arbor, MI discussed but did not enact such laws. (13)

   Though national legislation was not passed immediately, this in no way indicated a lack of national interest. Rather, national action needed consensus from the scientific community. For that reason, biologists, lawyers, physicians, government officials, and journalists (14) met at the Asilomar Conference on Recombinant DNA in February 1975 to draw up research guidelines. Believing that "[conference participants] were making public policy, and [that] they were making it in private," (15) Senator Ted Kennedy (D-MA) offered Congress' only legislative reaction in late 1975. The bill, (16) cosponsored by two Republicans, Richard Schewiker (R--PA) and Jacob Javits (R-NY), sought to form a commission to study scientific breakthroughs, including recombinant DNA advances. (17) While it failed to pass the Senate in 1975, it was not dead just yet. The NIH Director's Advisory Committee met in February 1976, in which "representatives of various public interest groups, representatives of various factions within the scientific community, and other interested parties" discussed the recently drafted NIH guidelines. (18) After this meeting, Senator Kennedy's bill passed the Senate in May 1976 but died in the House. (19)

   The uptick in Congressional attention to recombinant DNA towards the end of the 1970s was likely precipitated by the issuance of the NIH guidelines regarding such research in June of 1976. (20) While meant as a compromise, the guidelines did have not the calming effect intended. Rather, it brought to light that this technology was no longer theoretical frontier science, but had gained practical usage necessary to support government intervention and regulation. In the wake of the guideline's issuance, a number of legislators found them insufficient and sought to modify them statutorily. Moreover, as the Hastings Center argued at the time, an abbreviated timeline between preliminary discussions and promulgated guidelines--4 months--did not permit sufficient public input, even if the actual substance of the guidelines were satisfactory. (21) Subsequent dissatisfaction may therefore have been caused as much by procedural as substantive discontent.

   From the time the guidelines passed through the end of 1976 through 1978, only 14 unique bills were proposed in either House (3 were repeatedly considered with nominal changes). (22) Each was proposed by a Democratic lawmaker, and all but one enjoyed significant Democratic co-sponsorship (the lone exception only had one co-sponsor, a Republican). (23)

   Some of bills called for commissions to study scientific issues--neither limited to nor prioritizing recombinant DNA over other issues to be studied. (24) The proposed commissions varied in small but important ways, including size and appointment. (25) Other bills called for a regulatory framework to oversee recombinant DNA research projects via licensure and or grant programs under the NIH's direction. (26) These proposed schemes included penalties for violations, ranging in criminality, financial fines, and required scienter, or underlying mental state. (27) Interestingly, multiple bills whose primary purpose was a regulatory framework included provisions to create similar commissions. (28)

   Both Houses held hearings on a few of the bills proposed, and both the House and Senate held general hearings in 1977 to inquire about the overall status of Recombinant DNA research, the House in March, April, May, and September, (29) the Senate in November. (30) Ultimately, though, none of the above measures regarding recombinant DNA were signed into law in the immediate aftermath of the NIH's rules change. (31)

   It can be said that the legislative response to the evolution and progression of recombinant DNA was relatively modest--even muted--in light of a hugely impactful scientific breakthrough. The obvious question is why? It may have been in part because the ethical concerns were not especially significant, or that those in a position to affect change simply did not understand the scientific implications. A different explanation is that the science's significant promise was already apparent to the scientific community. For example, by 1978, scientists had discovered how to use recombinant DNA-based science to isolate and produce human insulin, replacing more expensive animal sourcing. (32) Thus, despite the ethical concerns made known by several prominent legislators, the lack of demand for regulation--potentially aided by the tangible advantages of this technology--may have outweighed the ethical considerations. Whatever the cause, it is fair to say that the ethical concerns of recombinant DNA never gained sufficient critical mass to persuade a majority of Congresspersons.

3. IVF (01/01/1978 - 12/31/1982)

   In 1969, Robert Edwards, Patrick Steptoe and their research team published a report that they fertilized human ova, the first steps towards in vitro fertilization. (33) After that initial study was published, Edwards published an article on the ethical implications of his research to assuage those who found the science morally questionable. (34) After publishing these two articles, however, there was little hoopla regarding the science of IVF, arguably because it appeared as if little work was being done in the field across the scientific community otherwise. The lack of work, though, was due in part to the United Kingdom's Medical Research Council "declin[ing] on ethical grounds" to use public funding for IVF research in 1971. (35) It is arguable that these ethical suspicions continued far into the history of IVF; indeed, some have speculated that this is what delayed the awarding Edwards the Nobel Prize until 2010 -- only Edwards would receive it, as Steptoe had passed and the award cannot be given posthumously. (36)

   The two scientists resurfaced with extraordinary advances in the field 8 years later. In 1976, Edwards and Steptoe published an article saying they had successfully impregnated a woman using in vitro fertilization, though it was an ectopic pregnancy. (37) Two years later, on July 25, 1978, Louise Brown, the first IVF child, was born in Oldham, UK. (38) IVF eventually crossed the pond to the United States in 1981, given Ms. Brown's conception in 1977, we review Congressional reaction spanning the 95th, 96th...