While advancements in biotechnology, genomics and high throughput screenings or combinatorial and asymmetric syntheses are opening new opportunities in drug discovery, the industry is facing serious innovation deficit. The total number of new molecules registered per year has dropped in contrast to expected increase. Post marketing failures of blockbuster drugs have become major concern of industry.
On the other side, globally there is a major shift to use of traditional medicine involving complementary and alternative therapies. Ethnopharmacology and traditional medicine have contributed significantly to the process of natural product drug discover in past. There are two clear tracks, where ethopharmacology has potential to contribute to future drug research - as a discovery engine to provide new targets and leads and as quality assured and standardised traditional medicines. In this scenario, it is important to understand the mechanisms of drug discovery and pharmaceutical development with a focus on herbal drugs and nutraceuticals.
Ethnopharmacology & traditional medicine
Numerous drugs have entered the international pharmacopoeia via the study of ethnopharmacology and traditional medicine. For traditional medicines, newer guidelines of standardisation, manufacture and quality control and scientifically rigorous research on the scientific basis for traditional treatments will be required. Traditional medicines can offer a more holistic approach to drug design and myriad possible targets for scientific analysis. Powerful new technologies such as automated separation techniques, high throughput screening and combinatorial chemistry are revolutionising drug discovery.
Traditional knowledge can serve as powerful search engine, which will greatly facilitate intentional, focused and safe natural product drug discovery and help to rediscover the drug discovery process. By looking at the historical trends in drug and medical developments, it is possible to understand how current drug development will benefit from this partnership.
Despite the small number of species sources explored yet, drugs derived from plants are of immense importance in terms of numbers of patients treated. It is reported that 25 per cent of all prescriptions dispensed from community pharmacies in USA between 1959 and 1973 contained one or more ingredients derived from higher plants. Besides, a recent study of the top 150 proprietary drugs used in USA found that 57 per cent of all prescriptions contained at least one major active compound currently or once derived from (or patterned after) compounds derived from biological diversity.
Financially, the retail sales of pharmaceutical products were estimated at US $80-90 billion globally in 1997, with medicinal plants contributing very significantly. A study of the 25 best selling pharmaceutical drugs in 1997 found that 11 of them (42 per cent) were biologicals, natural products or entities derived from natural products, with a total value of US $17.5 billion. The total sales' value of drugs (such as Taxol) derived from just one plant species (Taxus baccata) was US $2.3 billion in 2000.
Indian ayurvedic and traditional Chinese systems are living great traditions. These traditions have organised database and more exhaustive description of botanical material that is available and can be tested using modern scientific methods. Both systems of medicine, thus, have an important role in bioprospecting of new medicines. Good botanical practices which can improve the quality control procedures of monitoring impurities, heavy metals and other toxins in the raw material can make the ethnopharmacology research more meaningful.
Drug discovery in current scenario has become unproductive to the point where the economic future of the industry is questionable. To push into the future, the R&D thrust in the pharmaceutical sector needs to be focused on development of new drugs, innovative processes for known drugs and development of plant-based drugs through investigation of leads from the traditional systems of medicine. Traditional medicine can provide novel inputs into the drug development process. Yet, bioprospecting - the search for economically valuable natural resources - by pharmaceutical companies has not been conspicuously successful in recent years.
The R&D thrust in the pharmaceutical sector is focused on development of new drugs, innovative/indigenous processes for known drugs and development of plant based drugs through investigation of leads from the traditional systems of medicine. In addition, many nutraceuticals are being consumed from unregulated markets for their perceived benefits in healthcare and improvement of quality of life. Natural pharmaceuticals, nutraceuticals and cosmeceuticals are of great importance as a reservoir of chemical diversity aimed at new drug discovery and can be explored as potential antimicrobial, cardiovascular, immunosuppressive and anticancer drugs. Around 80 per cent of all such products are of plant origin and their sales exceeded $65 billion in 2003. Examples of plant products and derivatives used by the pharmaceutical industry include Paclitaxel, Vincristine, Vinblastine, Artemisinin, Camptothecin and Podophyllotoxin.
Natural products, including plants, animals and minerals have been the basis of treatment of human diseases. Modern medicine or allopathy has gradually developed over the years of scientific and observational efforts of scientists. However, the basis of its development remains in the roots of traditional medicine and therapies. The history of medicine includes many ludicrous therapies. Nevertheless, the ancient wisdom has been the basis of modern medicine and will remain as one important source of future medicine and therapeutics.
Even during the early part of this century, plants were a vital source of raw material for medicines. The future of natural product drug discovery will be more holistic, personalised and involve wise use of ancient and modern therapeutic skills in complementary manner so that maximum benefits can be given to patients and the community. A large number of molecules have come out of ayurvedic experiential base, including Rauwolfia alkaloids for hypertension, Psoralens in Vitiligo, Holarrhena alkaloids in Amoebiasis, Guggulsterons as hypolipidemic agents, Mucuna pruriens for Parkinson's disease, Piperidines as bioavailability enhancers, Baccosides in mental retention, Picrosides in hepatic protection, Phyllanthins as antivirals, Curcumines in inflammation, Withanolides and many other steroidal lactones and glycosides as immunomodulators.
Various institutions, including the Indian Council of Medical Research (ICMR) and Council for Scientific and Industrial Research (CSIR) in India, are taking another tack, exploring alternative paths to modern pharmaceutical research presented by traditional medicine that could be cheaper, faster and more effective. One such strategy involves a process known as reverse pharmacology, which begins with a useful natural product and works backward, as it were, to identify its active ingredients. CSIR has just concluded series of clinical trials on herbal products of medicinal value generated through reverse pharmacology, with several public and private partners. Looking at the future, it is important to consider the relative potential of these approaches to generating cost-effective and safe medical products.
For several reasons, the modern drug discovery processes have started revisiting traditional knowledge and ethnopharcacology to reduce the typical innovation deficit faced today. Traditional knowledge and experiential database can provide new functional leads to reduce time, money and toxicity - the three main hurdles in the drug development. These records are particularly valuable since effectively these medicines have been tested for thousands years on people. The Indian CSIR is playing an important role through public-private profiting partnerships in R&D in a very professional manner. It has received due appreciation from the corporate, scientific and governmental sectors for its programme New Millennium Indian Technology Leadership Initiative (NMITLI). In this programme of Government of India, a number of industry partners such as Nicholas Piramal, Lupin, Zandu, Dabur, Dhootpapeshwar and Natural Remedies, are part of.
Future perspectives
Looking forward, it is clear that traditional and western medicine have the potential for rich collaboration that benefits both disciplines. There is growing interest in this partnership, as shown by the number of international journals now dedicated to such research, such as Complementary Therapies in Medicine, eCAM, Alternative Therapies in Health and Medicine and the Journal of Alternative and Complementary Medicine.
Even the WHO has taken note of the rich possibilities of the future of traditional medicine, for instance 'WHO General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine' and 'WHO Guidelines on Good Agricultural and Collection Practices (GACP) for Medicinal Plants. Despite this enthusiasm, there are several areas where the international community will need to focus their attention, if the goal of integrating botanical medicines for the good of human health is to be reached.
(The author is director of Interdisciplinary School of Health Sciences, University of Pune).