A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity

Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources

Technological Change and Agricultural Development

Understanding the forces shape the rate and direction of technological progress is central to confronting key challenges facing the world today. Yet there is little systematic evidence on the factors that determine the evolving patterns of invention across applications, or the impact of these patterns on productivity and resilience in the face of shocks to production. The present set of essays investigates this topic, with an empirical focus on agriculture and the environment. Chapter 1: The first chapter investigates the impact of intellectual property enforcement on technology development and productivity. Patent protection was introduced for plant biotechnology in the United States in 1985, and it affected crops differentially depending on their reproductive structures. Exploiting this unique feature of plant physiology and a new dataset of crop-specific technology development, I find that the introduction of patent rights increased the development of novel plant varieties in affected crops. Technology development was driven by a rapid increase in private sector investment, was accompanied by positive spillover effects on innovation in certain non-biological agricultural technologies, and led to an increase in crop yields. Patent rights, however, could come with significant costs to the consumers of technology and distort downstream production. Nevertheless, I document that in US counties that were more exposed to the change in patent law because of their crop composition, land values and profits increased. Chapter 2: The second chapter investigates the extent to which innovation mitigates the economic impact of environmental catastrophe, focusing on the the American Dust Bowl, an environmental crisis that led to widespread soil erosion and production losses on the US Plains during the 1930s. Combining data on county-level erosion, the historical geography of US crop production, and crop-specific technology development, I document that the Dust Bowl led to a major shift in the direction of US agricultural technology toward more Dust Bowl-exposed crops and, within crops, toward bio-chemical and planting technologies that could directly mitigate environmental distress. County-level exposure to new innovation significantly dampened the effect of the Dust Bowl on land values and agricultural revenues. These results highlight the role of crises in shaping the direction of innovation and the importance of endogenous technological progress as an adaptive force in the face of disasters. Chapter 3: The third chapter, written with Karthik Sastry, studies how agricultural innovation reacts to modern climate change and shapes its economic impacts in the US. We show in a model that directed innovation can either mitigate or exacerbate climate change’s economic damage depending on whether new technology is on average a substitute for or complement to favorable climatic conditions. To empirically investigate the technological response to climate change, we combine data on the geography of agricultural production, shifting temperature distributions, and crop-specific temperature tolerance to estimate crop-specific exposure to damaging extreme temperatures; we then use a database of crop-specific biotechnology releases and patent grants to measure technology development. We first find that innovation has re-directed toward crops with increasing extreme-temperature exposure and show that this effect is driven by types of agricultural technology most related to environmental adaptation. We next find that US counties’ exposure to climate-induced innovation significantly dampens the local economic damage from extreme temperatures, and estimate that directed innovation has offset 20% of the agricultural sector’s climate damage since 1960 and could offset 15% of projected damage in 2100. Chapter 4: An influential hypothesis explaining the persistence of global productivity differences is that frontier technologies are finely tuned to the local conditions of the high-income countries that develop them and inappropriate for application elsewhere. The fourth chapter, written with Karthik Sastry, studies how environmental differences between frontier innovators and the rest of the world shape the global diffusion, adoption, and productivity consequences of agricultural technology. Our empirical design uses differences in the presence of unique crop pests and pathogens (CPPs) as a instrument for the appropriateness of crop-specific biotechnology developed in one country and applied in another. We first find that inappropriateness predicted by CPP differences reduces cross-country transfer of novel biotechnology. We next find that inappropriateness relative to frontier innovators reduces adoption of improved seeds and crop-level output. Our estimates suggest that the inappropriateness of the contemporary frontier reduces global productivity by 50% and increases cross-country dispersion in log productivity by 15% relative to a world in which technology were equally productive in all contexts. We use our framework to study how historical and predicted changes in the geography of innovation affect the global distribution of agricultural productivity.Ph.D

State Capacity and American Technology: Evidence from the Nineteenth Century

Robert Gordon's The Rise and Fall of American Economic Growth compellingly shows how technical innovation, stimulated by the country's institutions, has radically improved the living standards of the citizens of the US. We conduct an empirical investigation of the impact of the capacity of the US state, as proxied by the presence of post offices, on innovation. We show that there is a strong association between the number of post offices in a county and patenting activity. Our evidence suggests that part of story of US innovation is the capacity and reach of the US state

Segmentary Lineage Organization and Conflict in Sub‐Saharan Africa

We test the longstanding hypothesis that ethnic groups organized around “segmentary lineages” are more prone to conflict. Ethnographic accounts suggest that in such societies, which are characterized by strong allegiances to distant relatives, individuals are obligated to come to the aid of fellow lineage members when they become involved in conflicts. As a consequence, small disagreements often escalate into larger‐scale conflicts involving many individuals. We test for a link between segmentary lineage organization and conflict across ethnic groups in sub‐Saharan Africa. Using a number of estimation strategies, including a regression discontinuity design at ethnic boundaries, we find that segmentary lineage societies experience more conflicts, and particularly ones that are retaliatory, long in duration, and large in scale.</jats:p