CLINICAL MATTERS
The University of the Philippines National Institutes of Health’s (UP-NIH) recent win at a prestigious international competition in the US serves as a strong reminder that the Philippine government continues to support relevant health research in the Philippines. The double whammy of limited resources and a dense bureaucracy make obtaining meaningful funding for local research projects a veritable calvary for our Filipino scientists. Nevertheless, those that prevail have the potential to benefit millions of Filipinos with homegrown solutions that are tailormade for local problems.
As a research professor and institute director at the UP-NIH Institute of Molecular Biology and Biotechnology (IMBB), I have been a witness to how health research support has grown by leaps and bounds since I joined the institute in 2008. I came home as a long-term Balik Scientist of the Department of Science and Technology (DOST) following six years of training in the US.
At that time, the Balik Scientist endeavor was just a program at DOST and it had variable funding and could only support a limited number of scientists each year. As the program grew, the Philippine government recognized its accomplishments and its vast potential. In response, Congress enacted the Balik Scientist Law which ensured dedicated funding and continuity. Short term Balik Scientists of Filipino descent were able to return home for brief periods of time to build capacity, educate local researchers, and forge links between their institutions and local universities which have since resulted in many fruitful partnerships. Long term Balik Scientists such as myself received support for relocation and reintegration into the Philippine academic community. We were given research grants to establish our laboratories so as to hit the ground running.
The IMBB at the UP-NIH was established in 1994. In 1995, it became part of the network of National Centers of Excellence in Molecular Biology and Biotechnology. In 1998, it was one of the four founding institutes of the National Institutes of Health, which has since grown to 15 institutes and centers.
The NIH IMBB started off with humble beginnings with limited equipment and funding. The first two institute directors, Dr. Nina Gloriani and Dr. Bernadette Ramirez, laid the groundwork for expansion and have since gone on to illustrious research careers. In 2008, when Dr. Raul Destura took over as director, he embarked on an ambitious capacity building initiative. From an office with no furniture and the promise of an air conditioner, the beginnings of a word-class molecular biology laboratory complete with a BSL-3 containment unit began to take shape.
It was during this time that I joined IMBB and felt the energy and potential of the place. I had met Raul several years earlier at an infectious diseases conference in Toronto, Canada and immediately felt a kindred spirit. My research mentor, former DOH Undersecretary Dr. Vicente Belizario, introduced us, and said that if I made good on my promise to return home, he would hire me and have me join IMBB. Serendipitously, Dr. Belizario was the deputy executive director of UP-NIH when I did come home and he made good on his promise. Raul was in the midst of creating his innovative low-cost dengue kit (Biotek M) and building the first University spinoff (Manila Health Tek Inc.) in the Philippines to market the kit
The DOST secretary at that time, Sec. Estrella Alabastro, was embarking on an unprecedented expansion of research capacity in the country, more than doubling its budget for grants-in-aid for scientists to do basic and applied research. My very first grant, a project to look at HIV prevalence in different at-risk populations, had a modest budget, but it was a good start and generated useful data.
The A(H1N1) pandemic hit in 2009 and we were well-poised to study it at IMBB. We received a sizeable grant, with myself as principal investigator, to do molecular epidemiology and genomics on the pandemic influenza virus. We sequenced the greatest number of A(H1N1) specimens in the country at that time, and also served as an overflow laboratory to the Department of Health which was overwhelmed with requests for testing. We detected the first instances of oseltamivir resistance and presented this in international conferences. The pandemic influenza project was Raul’s brainchild, but since he was concentrating on his dengue work, he asked me instead to apply for it and we were successful.
Having successfully completed a large grant, I knew it was time to put together a program of study for the disease that was killing off young Filipinos at an increasingly alarming rate—HIV. There was a dearth of data on the basic epidemiology of HIV—molecular subtypes, resistance rates, treatment failure rates, and what was causing the number of cases to grow so quickly. We had published a self-funded paper showing that the subtype of HIV in the Philippines had changed from subtype B to a potentially more aggressive subtype CRF01_AE and we wanted to characterize this better.
In the process of studying HIV drug resistance, we had to set up an HIV drug resistance testing laboratory. At that time, only one laboratory in the entire country was doing HIV drug resistance testing—the Research Institute for Tropical Medicine—and they were swamped. After hearing me complain too many times about how long it took to get HIV viral resistance testing results, Raul pretty much ordered me to make our own at IMBB and we did. HIV drug resistance testing at that time required a sophisticated laboratory with an RT-PCR, the ability to sequence the HIV resistance genes, and knowledge in bioinformatics to interpret the results.
My program of study for HIV consisted of three parts: Acquired drug resistance in patients failing treatment after one year on antiretrovirals; transmitted (pre-existing) drug resistance in newly diagnosed HIV patients; and the development of a diagnostic to enable testing of HIV drug resistance without having to build a sophisticated laboratory. The first project produced important insights into what factors were involved in predicting treatment failure, what antiretroviral regimens were most durable, and what drug resistance mutations were most prevalent in the country. The second project established the baseline HIV drug resistance rates prior to treatment and definitively showed that CRF01_AE is more aggressive and transmissible compared to other circulating subtypes. Our data from the second project has been used by the World Health Organization for their local benchmarks.
The third project ended up winning Innovation of the Year at the recently concluded IDWeek in Boston, Massachusetts in the US. Using an innovative technique to simplify processing of HIV viral genomes and a portable sequencing machine known as a MinION, our home-grown portable HIV drug resistance test has the potential to improve HIV care not just in the Philippines but in many resource-limited settings around the world. Not bad at all for a research institute from a third world country. The next step is a clinical trial to fine tune the test for its commercial rollout. We look forward to partnering anew with DOST and the Filipino people in this endeavor, since they have both been with us on this journey every step of the way.