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Creating a Roadmap for Building a Sustainable Genomics Facility in the Philippines

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Philippine Journal of Science 148 (S1): 15-32, Special Issue on Genomics ISSN 0031 - 7683 Date Received: 19 Mar 2019 Creating a Roadmap for Building a Sustainable Genomics Facility in the Philippines Alexander T. Young* Philippine Genome Center University of the Philippines Diliman, Quezon City 1101 Philippines Genomics, bioinformatics, and high-throughput technologies provide a means to create breakthrough solutions for a remarkably wide diversity of fields – including medicine, agriculture, fisheries, livestock, and biodiversity. Significantly, the precision of genomics and DNA enable the creation of applications that are specifically optimized for the Philippines. Dissemination of these technologies throughout the country is accelerated by genomics facilities that provide access to core technologies. However, there are significant scientific and business challenges for creating a sustainable genomics facility in the Philippines. The historical successes and challenges of genomics and high-throughput technologies are reviewed, which point to potential solutions for creating a sustainable genomics facility in the Philippines. Keywords: bioinformatics, drug discovery, functional genomics, genomics, high-throughput DNA sequencing INTRODUCTION systems in order to find new applications that benefit society. In conjunction with the technological advances in biology New and exciting advances in genomics and high-throughput and engineering, advances in computational sciences have technologies are revolutionizing the application of biological enabled the daunting task of interpreting the massive amounts sciences. Advances in engineering, microfluidics, robotics, of data that these technologies generate (bioinformatics). and miniaturization have created machines that can rapidly The ability to profile thousands to millions of biological determine the DNA sequence of an organism’s genes or molecules in a massively parallel fashion promises to create the entire genome. Similar advances in miniaturization new biological insights that can lead to better medicines, have created machines that can rapidly test the activity of agriculture, fisheries, forensics, and molecular diagnostics. thousands of biological samples (high-throughput assays). All of these new technologies are available or being High-throughput assays can be used to screen libraries of developed at the Philippine Genome Center (PGC). thousands of chemical compounds for the identification of new drug molecules that combat disease (high-throughput The PGC was created by the Philippine government with screening). Technologies that simultaneously profile major funding coming from the Department of Science thousands of RNA transcripts to measure gene activity and Technology and Commission for Higher Education (transcriptomics), proteins (proteomics), metabolites “to create a deeper understanding and judicious application (metabolomics), and microorganisms (microbial community of advanced knowledge and emerging technologies in profiling/metagenomics) in response to disease, drugs, or the genomics and bioinformatics for the benefit of Filipinos environment promise to unravel the complexities of biological and the rest of humanity.” Located at the National Science Complex in the University of the Philippines (UP) Diliman *Corresponding Author: [email protected] campus, the PGC is housed in a newly constructed 5,600-m2 15 Special Issue on Genomics Young: Creating a Roadmap for Building a Sustainable Genomics Facility in the Philippines facility with the construction of a second 4,500-m2 building Table 1 depicts the top five best-selling prescription medicines underway. While PGC is part of the UP system, the PGC twenty years ago in 1998 when the Human Genome Project is intended for use by all Philippine entities – including was actively underway. Since drug development takes an public and private universities outside of the UP system, average of seventeen years – from initial basic research government agencies, industries, non-governmental discovery to product launch (Westfall et al. 2007) – Table 1 organizations, and collaborating institutes and companies reflects the trend towards mechanism-based drug discovery in other countries. in the 1980s as our understanding of molecular biology became more sophisticated. Hence, the most successful Research and development (R&D) at the PGC currently drugs revolved around the modulation of specific cellular engages in four programs: 1) health; 2) agriculture, targets that have been determined through basic research to livestock, and fisheries; 3) biodiversity and ethnicity; and be associated with specific disease pathways. For example, 4) computational genomics and systems biology. The PGC, the top-selling drug in 1998 was the peptic ulcer drug Prilosec the high-throughput technologies it offers, and the domain (omeprazole; approved in 1988), which lowers stomach acid expertise of numerous people can promote sweeping by blocking the action of a gastrointestinal proton pump. advances in these fields to benefit the Philippines and Table 1 also illustrates the use of biomarkers such as high society. The ability to identify and quantify thousands of serum cholesterol or high blood pressure as a metric for molecular biomarkers through genomics, transcriptomics, the use of cardiovascular drugs to treat atherosclerosis or proteomics, metabolomics, and other emerging “omics” hypertension. Statins like simvastatin (approved in 1992) technologies can create precision technologies that are treat atherosclerosis by modulating the enzyme involved tailored and optimized for Filipino patients, Philippine in cholesterol biosynthesis. Calcium channel blockers like crops, Philippine fisheries, and the Philippine ecosystem. amlodipine (approved in 1990) and angiotensin-converting This article discusses the successes and challenges of enzyme inhibitors like enalapril (approved in 1984) are used genomics and high-throughput technologies in the past to treat hypertension because both drugs modulate target and present, with a particular emphasis on how these proteins that regulate blood pressure. Previous drug discovery technologies can impact the Philippines in the future. was based upon relief of symptoms without an understanding of biological mechanism or drug targets. For example, the mechanism by which aspirin relieves pain and fever was not understood until it was later discovered that aspirin binds to HEALTH the target protein cyclooxygenase, an enzyme involved with Paradigm shifts in healthcare are already seen from the the synthesis of inflammatory prostaglandins. Human Genome Project and DNA sequencing technologies. The Human Genome Project became a platform for the These include paradigm shifts in the way that pharmaceutical discovery of new drug targets. Drug targets represent entire companies conduct R&D to discover new prescription generations of drug classes (e.g., statins, ACE inhibitors, medicines and paradigm shifts in the way that physicians calcium channel blockers). In 2006, shortly after the treat patients. The impact of the Human Genome Project and completion of the Human Genome Project, it was estimated DNA sequencing technologies on human healthcare can be that all 21,000+ known drugs (of which 1,357 were of illustrated by comparing the top-selling prescription drugs unique classes) exert their therapeutic effects by affecting before and after the Human Genome Project (Tables 1 and 2). Table 1. Top 5 selling prescription drugs of 1998. Brand Generic name Therapeutic area Target Platform Biomarker 1998 sales name (billion) Prilosec Omeprazole Ulcers and gastric Gastric H+/K+ ATPase Small molecule PHP 210.73 esophageal reflux disease (proton pump) (USD 3.9761) Zocor Simvastatin Hypercholesterolemia HMG-CoA reductase Small molecule Serum PHP 209.09 cholesterol (USD 3.9450) Prozac Fluoxetine Depression Serotonin transporter Small molecule PHP 149.04 hydrochloride (USD 2.8120) Norvasc Amlodipine Hypertension Calcium channel Small molecule Blood PHP 136.50 besylate pressure (USD 2.5750) Vasotec Enalapril Hypertension Angiotensin converting Small molecule Blood PHP 127.20 enzyme pressure (USD 2.4000) Source: Med Ad News (May 1999) 16 Special Issue on Genomics Young: Creating a Roadmap for Building a Sustainable Genomics Facility in the Philippines Table 2. Top 5 selling prescription drugs of 2017. Brand Generic name Therapeutic area Target Platform Biomarker 2017 sales name (billion) Humira Adalimumab Arthritis; Crohn’s disease, TNF Protein therapeutic, PHP 976.6 ulcerative colitis alpha human monoclonal (USD 18.427 billion) antibody Rituxan Rituximab Non-Hodgkin’s lymphoma; CD20 Protein therapeutic, CD20-positive PHP 489.6 chronic lymphocytic chimeric human- B cells (USD 9.238) leukemia; rheumatoid murine monoclonal arthritis (RA) antibody Revlimid Lenalidomide Multiple myelomas as Cereblon Small molecule PHP 433.9 maintenance therapy (USD 8.187) following autologous hematopoietic stem cell transplantation; transfusion- dependent anemia Enbrel Etanercept Arthritis; ankylosing TNF Protein therapeutic, PHP 417.9 spondylitis; plaque psoriasis chimeric dimeric (USD 7.885) TNF receptor – immunoglobulin Fc fusion protein Herceptin Trastuzumab HER2 overexpressing HER2 Protein therapeutic, HER2- PHP 394.4 breast cancer; HER2 humanized overexpressing (USD 7.441) overexpressing metastatic monoclonal antibody breast cancer gastrointestinal cells adenocarcinoma Source: Philippidis (2018) only 266 targets encoded by human genes (324, including drug target
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