WHY MALAYSIA SHOULD EMBRACE NEW PARADIGM FOR DRUG DISCOVERY BY USING ROBOTIC TECHNOLOGY

“…….that drug discovery from our biodiversity is an imperative that cannot be postponed or stymied because of our own megalomania and persecutory complex that tends to over-protect our biodiversity. Malaysia’s healing gift to the world today may just come from the richness of our biodiversity but that can only be realized through research collaboration of scientists from both resource-rich and technology-rich nations of the world.”

The rainforests and the coral reefs of the tropical regions have been estimated to contain one-half to two-thirds of the world's biodiversity. They thus should be particularly rich sources of pharmaceutical agents. Yet less than 1% of rainforest plants have been studied for their pharmaceutical potential. Since the Convention for Biological Diversity, signed in Rio de Janeiro in 1992, there has been a greater appreciation of the value and benefits that can be derived from biodiversity. Among issues that have been contentiously pursued by biodiversity-rich countries were those pertaining to ownership and access to genetic resources, which converged into an agreement by 150 nations, including Malaysia, that biodiversity is a sovereign national resource. Essentially, this infers that in any attempt to exploit this biodiversity resource, as in the case of drug discovery, both suppliers and receivers should benefit economically.

The provision of royalties to the resource-rich country is frequently cited as a means of providing incentive for conservation of rainforests or coral reefs. In reality, the possibility of royalties derived from a new drug, for instance, may not provide sufficient incentive to the scientists or the host country involved. These participants often get discouraged because, as in other research-based venture, there is no guarantee of success. Even taking a very optimistic view, the usual paths and time taken for the eventual development of a new drug are often too slow, cumbersome and expensive. It has been estimated that as many as 10,000 to 50,000 compounds are screened for every commercially valuable drug that is discovered. Further, it may take as long as 12 years from the time of 'lead' discovery was made to obtaining the regular clearance for a prescription drug. Most prohibitive of all factors for any biodiversity-rich country venturing into drug discovery programme is the overall cost for R&D which often runs to more than US$250 million for a single drug. But a more likely guarantee for a lasting and visible benefit for these resource-rich countries is the enhancement of infrastructure through education and training, technology transfer and the provision of specialized equipment.

There is a clear need for intensive effort to discover new and inexpensive drugs from our rich biodiversity resource. Being young and still at a stage of fending for itself with respect to drug discovery, Malaysia is often faced with constraints that mitigate against a full development and growth of its own research capability. In recognition of the need to continually increase and strengthen its research capability, Malaysian scientists are encouraged to forge strategic alliances with many foreign universities and research organizations. Partnership with universities and institutions that have a strong tradition and capability in scientific discovery of drugs from biological resources must take priority. Particularly exciting is the international tie up with research organizations that have been using robotics to screen hundreds of thousands of compounds annually using a procedure called high-throughput screening (HTS). It is the process by which large numbers of compounds can be tested, in an automated fashion, for a variety of biological and pharmaceutical activities. HTS is capable of testing over 50 times as many samples for basic biological activity, largely due to investment in robotics and miniaturization. The greater the number and diversity of compounds that are run through a screen, the more successful it is likely to be. Today, fully automated robotic technology can screen 50,000 samples a day, or around 2.5 million samples each year. Miniaturization has also lowered the cost of screening, as the cost of running assays depends substantially on sample volumes.

In recognizing that HTS is the way forward in future drug discovery, Malaysian scientists should be encouraged to forge smart partnership with several research organizations locally and abroad to utilize this robotic technology. Together they can work collaboratively in the collection and identification of microorganisms and plants from both the coral reefs and tropical rainforest ecosystems. Our research efforts should concentrate on a variety of pristine and unique habitats found in conservation areas of Sabah, Sarawak and Peninsular Malaysia. An extract bank should be developed at the national level where chemicals and compounds isolated from our diverse terrestrial and marine species are preserved and systematically coded for scientific investigations. These biological extracts can be screened for a variety of pharmaceutical activities by all interested parties and investigators locally and internationally. The high-throughput screening by robotic technology include bioassays for antimicrobials, anti-inflammatory, anti-cancer, enzyme inhibitor, apoptosis suppression inhibitor, tumor growth factor, cardiac receptor antagonist, platelet aggregation inhibitor and an array of other medically relevant reactions and pathways. Out of these thousands of extracts, ‘hits’ obtained would require further elucidation and development before any of them eventually end up on the shelf of our pharmacy. Such high rate of screening success can only serve to remind us that drug discovery from our biodiversity is an imperative that cannot be postponed or stymied because of our own megalomania and persecutory complex that tends to over-protect our biodiversity. Malaysia’s healing gift to the world today may just come from the richness of our biodiversity but that can only be realized through research collaboration of scientists from both resource-rich and technology-rich nations of the world.