Day 1 :
University of Kentucky, USA
Time : 09:00-09:25
John Littleton studied Pharmacology and Medicine as an MD PhD student at Kings College, London University in England. He continued academic research at Kings College, mostly in CNS target validation, as a Professor in the Pharmacology Department until 1993. At this time he spent a year at the University of Kentucky on a Wellcome Foundation fellowship where he started to develop an interest in novel technologies for plant drug discovery. He returned to Kentucky in 1995 to further develop the plant drug discovery aspect of his research, using novel methods of mutagenesis and high throughput screening in plant cell cultures. He co-founded the biotechnology company, NaprogenixInc, in 2002 to commercialize these methods. With support from NIH (SBIR/STTR awards) and Kentucky (matching funds for these) Naprogenix and the University of Kentucky have refined the technology to its current state. The technology now utilizes the expression of protein targets in plant cells, followed by mutagenesis and selection for clones generating metabolites which interact with the target.
Plants are capable of synthesizing bioactive compounds with a complexity beyond current chemical synthesis. The pathways to these metabolites have evolved over millennia because they confer a survival advantage on individuals within the plant species. For example, many bioactive metabolites have evolved to be targeted on key proteins in the nervous system of herbivorous insects, so that ingestion of plant material disables the insect. Individuals with mutations that favor the production of this metabolite therefore survive and reproduce, because they are less likely to be eaten by the insect. This Darwinian evolution by natural selection has strong parallels with pharmaceutical R & D in which combinatorial chemical synthesis (CCS) is used to “evolve” a library of compounds toward a key therapeutic target protein, with “selection” by high throughput pharmacological screening (HTPS) for activity at this target. If we could persuade plants to redirect their extraordinary biosynthetic capacity toward target proteins that are valuable to us rather than to the plant, then plants might once again become important players in pharmaceutical R & D. This is theoretically simple. First we express our therapeutic target protein in plant cells and devise a procedure in which these transgenic cells will survive if they are producing metabolites which have the required activity on the target. This is our (un)natural selection pressure, which also mimics selection for target activity by HTPS. Then we create a population of the transgenic cells with random gain-of-function mutations (mimicking a CCS library) and expose them to the unnatural selection pressure. Those mutant transgenic cells which survive should therefore be highly enriched in individuals that are over-producing metabolites with the required activity at the therapeutic target protein. Some of these will be normally present in the wild-type plant but, because random gain-of-function mutagenesis can switch on genes which are normally quiescent, some of the active metabolites will probably be “novel”. If so, this “target-directed evolution” of plant biosynthesis will have generated novel medicinal plant cells with unique mutations that result in a specific pharmacological phenotype. This provides protection of IP in several different products in addition to novel active compounds. Thus, the mutant cells themselves can become production systems for active metabolites that are too complex for synthesis, and the genes which have been activated can be identified and used for genetic engineering of the same or other plant species. So far, proof of concept studies have successfully used several different plant species transformed with target proteins including human nuclear receptors, enzymes and transporter proteins. One of these, the generation of metabolites which inhibit the human dopamine transporter in mutant Lobelia cultures, will be discussed in detail later. This technology is therefore capable of “telling” plant cells to biosynthesize metabolites with activity at specific therapeutic target proteins. It has the great advantage of accessing the whole genomic / biosynthetic potential of a plant species. It qualifies as green chemistry in requiring only the normal chemical constituents of plant cell culture medium as the starting materials.
University of Vienna, Austria
Time : 09:25-09:50
Lothar Brecker received his diploma and PhD in Chemistry from the University of Dortmund in 1993 and 1996, respectively. After working at Graz University of Technology and Research Center Borstel, he became an Associate Professor at the University of Vienna. There he actually serves as Vice Dean of the Faculty of Chemistry, Director of the Chemistry Studies Program and Deputy Head of the Department of Organic Chemistry. His main research activities are in the fields of using NMR to study enzyme ligand binding, interactions between small molecules, and structure determination of natural products. He has published 90 papers in reputable journals.
Green Chemistry and sustainability in Chemistry are important topics since more than two decades. A couple of standards and public regulations have been defined, in particular in industrialized countries. The chemical industry nowadays checks their processes and activities with respect to sustainability. Frame conditions for these developments, however, differ entirely between different nations. Several local and regional aspects require diverse applications in the design of effective sustainable concepts. Hence globalization of Green Chemistry cannot be based on an application of a single standardized plan. Rather a globalized basic frame of targets should be aspired to reach the collective good. In realization regional aspects have to be considered. They should intend optimal applications of sustainability with respect to environmental, national and political frames. Reaching such globalized way of thinking can, however, not been managed within a few years. It is necessary to agree on globally long-term concerted approaches, which incorporate various regional necessities. And it is essential to globalize the ideas of sustainability and worldwide interactions, which will be generally accepted and regionally applied.
President and Chief Technology Officer Warner Babcock Institute for Green Chemistry, USA
Time : 09:50-10:35
John C Warner is the recipient of the 2014 Perkin Medal, widely acknowledged as the highest honor in American Industrial Chemistry. He received his BS in Chemistry from UMASS Boston, and his PhD in Chemistry from Princeton University. After working at the Polaroid Corporation for nearly a decade, he then served as Tenured Full Professor at UMASS Boston and Lowell. In 2007 he founded the Warner Babcock Institute for Green Chemistry, LLC where he serves as President and Chief Technology Officer, and Beyond Benign. He is one of the founders of the field of Green Chemistry, co-authoring the defining text Green Chemistry: Theory and Practice with Paul Anastas. He has published over 200 patents, papers and books. His recent work in the fields of pharmaceuticals, personal care products, solar energy and construction and paving materials are examples of how green chemistry principles can be immediately incorporated into commercial relevant applications. He received The 2004 Presidential Award for Excellence in Science Mentoring, the American Institute of Chemistry\\\'s Northeast Division\\\'s Distinguished Chemist of the Year for 2002 and the Council of Science Society President’s 2008 Leadership award. He was named by ICIS as one of the most influential people impacting the global chemical industries. In 2011 he was elected a Fellow of the American Chemical Society and named one of “25 Visionaries Changing the World” by Utne Reader.
People often discuss “barriers” to the implementation of green chemistry. This leads to the impression that there is some form of “push back” in the market for sustainable technologies. However, if a technology has attractive performance and cost attributes, it is unlikely that the additional presence of “sustainable” attributes will inhibit its adoption. Most often the “push back” in the market is related NOT to the sustainability aspect, but to the absence of sufficient performance and cost aspects of a product. History has shown us that for a technology to be successful in the market place, it cannot depend solely on its “sustainability” but must also be consistent with the traditional drivers. Developing successful green chemistry technologies therefore is fundamentally a challenge in innovation at the molecular level. An important reason why technology organizations have a difficult time meeting this challenge is because most academic chemistry and materials science programs do not adequately teach students techniques to help them design products that are sustainable. Universities around the world are finding ways to add the principles of green chemistry into their curriculum, and one day most, if not all, scientists will have the adequate training - but this will take several years. Until the entire chemistry workforce is fully trained in green chemistry, those organizations who have internalized green chemistry for themselves will enjoy significant competitive advantage. This presentation will discuss steps that companies at all positions of the supply chain can take to ensure that they get to, and stay at, the cutting edge of green chemistry.