Charting new waters in the quest for new drugs

The road to drug discovery

We often hear about the road to Olympic gold every time there is the winter or summer Olympics, chronicling the journey of athletes as they go on their quest for the elusive Olympic gold. Some scientists also have a quest for a different gold — for a drug that could potentially alter the lives of people all over the world. But what does it take to embark on the road to drug discovery? This road is filled with stories of both success and failure — from those becoming blockbuster drugs to some getting pulled out from the market. Drug discovery involves a lot of hard work, good hypotheses, and an ounce of luck would not hurt as well. Bringing a molecule from the laboratory bench to the patient bedside can take at least 15 years and costs billions of pesos. It seems to be a farfetched dream, but it is not impossible. And with the Philippines being in the apex of the center of marine biodiversity, we are presented with a rich source of possible new drug entities.

Yes, the next blockbuster drug may come from the sea. Nature has been one of the most successful sources of new drugs. Open your medicine cabinet and you will be likely holding a medicine from or inspired by Nature’s creation. Aspirin for pain and inflammation, quinine and artemisinin against malaria, the antibiotics erythromycin and penicillin and anticancer drugs paclitaxel and etoposide are among a few examples. The first generation of drugs from Nature was sourced mainly from terrestrial macro- and microorganisms. But with the significant improvement in technology for underwater exploration, purification and synthesis of natural products, drugs from the sea have begun their debut. Among these are Prialt for pain and the anticancer drugs eribulin mesylate, trabectedin and brentuximab vedotin, all released in the last 10 years.

But just how do we scour the sea for new drugs? Much of the success in finding new chemical entities is recognizing where to start, knowing your organisms, and how they interact with one another. It has recently become apparent that the true producers of high value compounds are microorganisms living in close relationship with macroorganisms such as sponges or mollusks. The process of finding the interesting molecules is also seeing significant technological improvements. Miniaturized assay systems with high-throughput capabilities can now rapidly weed out the interesting chemistry from the haystack of other molecules. There is also a lot of synergy among various thematic fields: chemistry, molecular biology, medicine and pharmacy, together with the fields of “omics” (genomics, transcriptomics and proteomics), aiming to understand how molecules work and mitigate diseases and identify potential side effects. Critical to bringing a molecule to the clinic is defining both the intended and unintended effects, with the goal of minimizing the latter.

The Marine Science Institute has a long-storied and successful journey in drug discovery from the sea, with several research programs instituted in the last decade. Among these are the National Cooperative Drug Discovery Group (NCDDG) in collaboration with the University of Utah, the Department of Science and Technology-funded Antibody and Molecular Oncology Research and the PharmaSeas research programs and the Philippine Mollusk Symbiont-International Cooperative Biodiversity Group in cooperation with University of Utah, Oregon Health and Sciences University, Ocean Genome Legacy (now part of Northeastern University) and Academy of Natural Sciences of Philadelphia (now part of Drexel University). These research programs have highlighted the potential of a wide array of marine organisms as sources of molecules with interesting chemistry and pharmacology.

Natural products research has been a productive and successful research area in the Philippines. To ensure the continuous development of this research theme in the country and align ourselves with the evolving global trends in natural products research will involve continuous learning and improvements in finding small molecules, and understanding diseases and how they can be modulated. It is a good combination of basic and applied research that can lead to a successful drug development endeavor. Here in the Philippines, it also involves capacity building of our researchers and enhancements in research facilities, equipment and techniques.

In the end, the aim is to make new drugs, but it should not be forgotten that new innovations — like novel ways of combating disease by understanding their biology — are also part of the goal. It should also not be taken for granted that as we realize the potential of Nature to provide cures and improve human health, we have the responsibility to conserve and ensure sustainable development of these resources.

Where the waves will take us

It is a privilege to be part of the long tradition of excellence in marine natural products at MSI. As an incoming faculty last year, I pondered the secret formula of MSI’s success. And it is actually not a very difficult equation. A simple one in fact: P+P+P= success, an additive combination of the Philippines, people power, and partners will surely hit the target.

The Philippines as an archipelagic nation sitting right at the heart of the Coral Triangle is perhaps our greatest asset that cannot be matched. The uniqueness of the Philippines coupled with our next P — people power — the MSI manpower provides the necessary expertise. The faculty, our graduate students and support staff form a strong team aimed at making innovations and discoveries in the marine sciences. But it is not merely a collection of warm bodies that fill up the room with their expertise, the MSI people power also comes along with the enormous passion and pride for what we do. And of course, a huge contributor to our success is our partnership with all of you, the local community, national and international agencies, NGOs and universities both here and abroad.

As they say, life begins at 40 and at MSI, we begin charting new waters. The rapid advancements in technology and methods will provide us with opportunities to obtain a global picture of the ocean and yet understand it from the tiniest molecular or cellular detail. This further bolsters an integrated multidisciplinary research that MSI has always stood for. We will have an increased synergy among the various thematic areas of marine science — physical, chemical, biological, and biotechnology — geared not only to innovate and discover, but also to provide answers and guidance on relevant issues that we confront as an archipelagic nation. The complex ocean dynamics will pose new sets of questions on how, why and what will happen to the ocean and its resources in the next 10, 20 or 30 years.

There will be opportunities to venture new avenues, and however different — or daring — the scientific questions we will have in the coming years, we will have the same commitment beyond 40 years. We will uphold the long revered tradition of honor and excellence and continue to be a bastion of academic and research excellence here in UP, the Philippines and Southeast Asia. We are committed to training the next generation of leaders in marine science, just like our mentors did for us. And of course, we are dedicated to be of service to the country, for sustainable development and conservation of our unique marine treasures. To accomplish all these, we will again require the 3P’s, the Philippines, our people power and you our partners. So we thank you all in advance for your continued and unwavering support and partnership with MSI. Mabuhay po kayo!

* * *

Lilibeth A. Salvador-Reyes, Ph.D., is an assistant professor at the Marine Science Institute. She recently obtained her Ph.D. in Chemistry from the University of Florida. She combines her research interests in marine natural products and molecular pharmacology toward finding new lead compounds for drug discovery and elucidation of the ecological roles of small molecules from marine organisms. Part of this article came from the closing remarks that she delivered as MSI’s newest faculty at the MSI@ 40 celebration in March 2014. E-mail her at [email protected].