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We like to think that courts are, and have always been, the primary and final interpreters of statutes. As the conventional separation-of-powers wisdom goes, legislatures "make" statutes while judges "interpret" them. In fact, however, legislatures across centuries of American history have thought of themselves as the primary interpreters. They blurred the line between "making" and "interpreting" by embracing a type of legislation that remains overlooked and little understood: "expository" legislation--enactments that specifically interpreted or construed previous enactments. In the most exhaustive historical study of the subject to date, this Article--the first in a series of Articles--unearths and explains that lost tradition of legislative statutory interpretation from an institutional perspective. To do so, it draws on an original dataset of 2,497 pieces of expository legislation passed from 1665 to 2020 at the colonial, territorial, state, and federal levels--the first effort of its kind. It shows how expository legislation originated as a colonial-era British import that Americans came to rely on beyond the creation of new constitutions. Lawmakers used expository statutes to supervise administrative statutory interpretation and to negotiate interpretation in the shadows of courts. Judges accepted and even encouraged legislative statutory interpretation. In the mid-nineteenth century, judges increasingly fought back, emboldened by growing calls for judicial independence. Yet even as the backlash entered into treatises, and even as some lawmakers began to balk, legislatures and judges continued to accept and use legislative interpretations of statutes well into the nineteenth century. The early history of expository legislation offers an alternative constitutional vision to the oft-repeated notion that statutory interpretation is necessarily and has always been an intrinsically and exclusively "judicial" power. As the Article ultimately argues, strict and formalist conceptions of separation of powers in statutory interpretation are misguided, for the extent to which statutory interpretation was considered a judicial power has fluctuated in ways that were intertwined with broader transformations in American society. This history teaches us to think of statutory interpretation as a shared task among branches but exercised in different contexts and domains. It also illuminates the historically contingent nature of legislation, revealing new ways that statutes can contain an inherent interpretive openness. These particular forms of openness raise new questions about the validity of subsequent legislative history. They also reveal how legislatures have embraced a paradoxical concept of original intent and meaning--one that legislatures recognized was rarely a "pure" kind but more often a fictional, dynamic kind intertwined with the changing views of post-enactment interpreters. [ABSTRACT FROM AUTHOR]

Opioid Use Disorder (OUD) is a significant public health issue in the United States and globally. FDA-approved treatment for OUD includes Opioid Substitution Therapy (OST) with medications such as methadone and buprenorphine. While OST has been shown to be effective, a meta-analysis of outcome data from OST studies indicated that a significant percentage of opioid dependent patients treated with OST do not sustain abstinence or reduce their illicit opioid use. Understanding the factors that predict reductions in illicit opioid use during treatment would allow clinicians to make more informed therapeutic decisions, selecting medications that are most likely to benefit individual patients. The START trial was a 24-week open-label randomized trial of methadone and buprenorphine for the treatment of OUD. Weekly urine drug screens were performed. Treatment efficacy was defined by the proportion of opioid positive urine tests. A Generalized Estimating Equation (GEE) was used to determine if variants in the OPRD1 gene were associated with treatment efficacy in African-Americans (AA; n=77). A replication population (n=75) was collected from AA patients who had previously participated in OST trials in Baltimore. Urine drug screens were performed three times per week. For a meta-analysis, weeks 21–24 were analyzed since they represent the last month of data available for both data sets. Responders were defined as patients who a) were retained in treatment until at least week 21 and b) were opioid positive for less than 50% of their urine drug screens in weeks 21–24. For in vitro analysis, 15 bp regions surrounding the C or T allele of rs678849 were cloned into luciferase vectors and transfected into neuroblastoma cells. Luciferase activity was measured by dual-luciferase reporter assay system. In the START trial, rs678849 was associated with the efficacy of methadone (p=0.001) and buprenorphine (p=0.008) in treating OUD in AA patients. The pharmacogenetic effect on buprenorphine (p=0.01), but not methadone (p=0.23), was replicated in the independent AA population from Baltimore. In a meta-analysis of weeks 21–24 of both data sets, patients with the C/C genotype had a significantly higher proportion of opioid positive urine drug screens (59%) than T allele carriers (26%, p<0.0001). Patients with the C/C genotype were also significantly less likely to meet responder criteria (27%) than other patients (64%, p=0.007). The number needed to treat (NNT) was 2.8 for the response analysis. Functional analysis in neuroblastoma cells by luciferase assay found that the vector containing the C allele had lower luciferase activity than empty vector. In contrast, the T allele vector had significantly higher luciferase activity than the C allele or empty vector. These data suggest that a variant in the OPRD1 gene has a large pharmacogenetic effect on buprenorphine efficacy in the AA population and that the variant may have effects on expression. We hypothesize that the C allele of rs678849 functions as a silencer element, binding transcriptional repressors and downregulating OPRD1 expression. We also hypothesize that the T allele of the variant is an enhancer element and upregulates OPRD1 expression through interactions with a unique group of transcription factors. Further in vitro studies will be needed to dissect the complete mechanism and a prospective clinical trial that confirms this pharmacogenetic effect will be necessary before rs678849 can be used to guide treatment decisions. [ABSTRACT FROM AUTHOR]