Fishing in the 'Sea of Drug Discovery': The Elusive Big Fish

Research endeavors to discover and develop new chemical entities, followed by  developmental work and integration with business to enable candidate drug enter the market as a new commercially viable therapeutic agent, is a difficult terrain. 

Before I deal with the subject in this inaugural post of the blog, allow me some interruption.

First and the foremost, let me explain, why this blog?

I have worked for over thirty years in a drug research organization, and writing has been central to  the most of my functions. Thus the compulsion of writing has narrowed down to the choicest field of drug research. Though, the other three blogs I run are in different domains; the one on biodiversity is out of my deeper interests in biology and evolution, the next on new found interest in advocacy in prevention and control of non-communicable diseases (NCDs), and the fourth one on career.

Research  and development of new drugs, diagnostics, and preventive therapies, together constitute a domain which assumes a special place due to its direct relevance and impact on human health. Undoubtedly, the advent of vaccines, antibiotics and other new drugs and health interventions, made possible as a result of scientific advances in biology and biomedicine, are singularly responsible for the increase in life expectancy over the  last century.

A peep into a pharmacy offers an intriguing view: so many drugs lined up on shelf, each preparation different from the other in their constituents, mechanism of action, therapeutic use, dosage, delivery, for use in adults, women, men, and children.......and in side effects(?). Interestingly most of them are novel innovative products. Physicians prescribe those medications confidently, patients use them with ready acceptance, and pharmacists sell them with smile. There is a win-win situation for all stakeholders in this innovation chain of new drug research and development.

How all this has been made possible? Great men of science, entrepreneurs, men of industry collectively have invested their time and money to make it possible. They were not hollow scientists grandising their achievements but proved the worth of their research investment for development of ultimate products which now sit on pharmacy shelves, and are written in doctors prescriptions. Drug research earlier considered a field marred by chance findings (serendipitous discovery of novel molecules), has of late become a more organised knowledge-based endeavour, and is evolving further.

With each passing day, drug research and development evolves along with the growing body of  knowledge of the basic understanding of the functioning of a healthy or diseased  body parts, the tissues and cells. Thanks to rapid advances in tools, techniques, and the competence of  trained scientists, and emerging disciplines of translational research, the era of tailor-made medicine are adding new opportunities as well as posing new challenges.

Scientists engaged in drug research are now deploying emerging tools and techniques made possible due to advances in genomics, proteomics, structural biology and other emerging disciplines which offer new opportunities for discovery of better drugs. Claims are made for discovery of new genes, proteins, markers, novel biological targets, etc. and these are associated with a big finding (in future). Institutions are spending all their focused efforts on discovery of new targets as aid to develop new drugs. 

The domain of drug discovery is now like a large sea, and the organizations and industries engaged in drug discovery are fishing in the  sea of those resources of unfathomable dimensions, leading to emerging new knowledge, for new starting points or leads; following those emerging trails, rough weather, waves and currents, in hope and desperation, to catch a big fish, a blockbuster drug, they travel far and wide. For, once they have the catch all costs will be recovered, huge profits made, and ailing humanity served, with a new drug. Then, there will be time to celebrate the big catch!

However, linking every new development to discovery of a new drug is however  a far cry, as the outcome from drug discovery and development research is possible only if an integrated effort is pursued in a  multi-disciplinary and multi-institutional framework right from the beginning, and is part of overall planning. No piecemeal approach is expected to lead to a drug. In any case, the ultimate success in drug discovery is not  achieved unless the candidate drug passes through the vigilant eyes of dedicated preclinical and clinical scrutiny, and it stays in the market without unwarranted adverse reactions.

High quality  basic research ranking high on 'high impact factor' publications may not always transform into new drugs. Though it does create a wealth of knowledge so important in drug discovery and development; more directly though it leads to research papers and patents fuelling scientists' journey to a better career, prestige, position, and pride of achievement! No doubt the need for basic research, opening new vistas of opportunities, is  fundamental to advancements and is the most necessary aspect to begin with.

A recent study does throw light on this aspect. It has been found that in spite of growing investment in pharmaceutical R&D the new drugs are not emerging. The reasons are that investments are concentrated in areas where failure risks are higher, and in use of tools and technologies not known to lead to new drugs.

Searching a target, its validation, its actual deployment in drug discovery will not necessarily lead to new drugs. Organisations having the objective to develop new drugs may know it better, but scientists out of their compulsion to build their CV and fuel their career advancements by decorating them with awards and honors, recognitions, etc,  adopt  a publication strategy, instead of a product oriented research approach.

Basic research remains only a pleasure trip unless the journey concludes to a logical end and a  new, safer and efficacious drugs emerge from the rigorous, expensive and time consuming enterprise of drug R&D, for the benefit of ailing men unattended by existing therapies, and for the service of humanity, and the society. And, there are always huge profits to reap from a novel blockbuster drug for the investment made on R&D.

Investment of now over US $ one billion mark is prohibitive for new drug discovery, and few can afford the innovative R&D workload unless it is shared through strategic alliances. New drug discovery R&D works well with both the ends open: through upward and backward integration. Integration is pursued all through the innovation change, that is discovery of molecule, its evaluation for activity through  in vitro and  in vivo systems,  physiology, pharmacology, dosage evaluation, delivery systems, toxicity studies and rigorous clinical evaluations.

Drug R&D  follows business strategies adopted by the leading pharmaceutical companies. What are those aspects which can ensure better drugs' outcome: planning, business strategy formulation, infrastructure, networking with concerned groups, integration and filling of knowledge gaps. A business plan needs to be prepared beforehand  a project is launched.

 The strategies include partnering on promising compounds for development of pipeline of products, outsourcing of different R&D stages in product development,  extending life of an aging brand, expanding into emerging markets, as well as focusing on internal packaging and delivery mechanisms, etc.

In India where there is a large livestock we seldom hear of any R&D organization working for development of  drugs for farm animals, or pets. (If I am ignorant I will like to be corrected). Most new veterinary products we have are the result of R&D abroad. Though there are companies in India making and distributing drugs for livestock and pets.

My association with a drug research institute has left me amused as to the total apathy towards the urgent need to develop drugs for diseases of the livestock, poultry, pets. Even if as  spin off, there ought to be some projects to attend to livestock diseases. We can not leave guessing if research and development of drugs for farm animals is left out from the agenda for reasons that drug research for human needs  is more fashionable or respectable, than drugs for farm animals? Veterinary medicines are indeed a bigger R&D challenge? Healthy livestock is related to health of humans!

Drug research is a hard-core scientific endeavour, and successes depend upon passion for research, knowledge, hard work, availability of funds, infrastructure, ability to network and establish linkages with organisations and industry  which share the collaborator's vision. Work ethics,  business processes used, issues of the availability of quality systems, and trust are of no less concern.

Slogans, big and false claims do not help in science-driven drug research. The bogey of  MNCs versus indigenous R&D, and industrial productivity, often raised, make no sense if we continue with our dependence for new drugs discovered and developed by them. Our pride however rests mainly in our  ability to produce quality generics at cheaper cost. 

Non-communicable diseases (NCDs) are assuming greater importance internationally, so much so that they now endanger the developing world economy by their increasing hold on their populations; pharmaceutical companies are constructing healthy pipelines in areas of heart disease, cancer, and diabetes, besides other diseases. Industry experts agree that the costs to develop new drugs are rising rapidly. The rapidly increasing costs that go into the R&D of promising new medicines make it a great challenge to develop new drugs that are affordable to the patients who need them!

As this blog develops and takes shape over time, I shall welcome any advise on the contents of this blog. Errors, omissions, and contradictions, if  inadvertently appear, and are pointed out to me will be readily corrected. My efforts shall be to constantly upgrade the blog to serve the drug research community!

As I conclude, I invite the industry and organizations engaged in drug research to forward their latest achievements and discoveries to me (zakaimam@gmail.com) for inclusion in this blog. Developments that merit coverage will find speediest place as a post.