Sunday, May 24, 2009

Google Wikipedia Chemical Library For Modern Medicine

I GOT THE ABOVE IMAGE FROM HERE.

Mention the words, modern medicine and the words "MAGIC BULLET" spring to one's mind. These two magic words sum up the end point of modern medicine. When faced with a disease management problem, modern medicine dips in to the magic box of research to bring out a brand of a MAGIC BULLET (molecules that selectively target bacteria or may be some disease causing agent) that will help resolve the disease. This summarizes the approach of modern medicine.

Dr. Paul Ehrlich pioneered the magic bullet approach. His seminal work on syphilis, TB and other diseases laid down the foundation for the pharmaceutical industry. Alexander Fleming too did new paradigm work with his serendipitous discovery of penicillin and his work on lysozyme. It would not be an exaggeration to say that the research work of these two gentlemen created the basic approach of the modern pharmaceutical industry.

What Paul Ehrlich and Alexander Fleming did was to usher in a particular way and thinking for creating new drugs. The process involved screening chemicals (synthetic and natural) and identifying their health benefits. Antimicrobials that interfere with protein synthesis of pathogenic bacteria - for instance, is an example of this approach. This approach has yielded many molecules that have conferred health promoting benefits to the world. And what this approach has also done is, it has helped create BLOCKBUSTERS.

Blockbusters have been created using the SAR (structure - activity relationship) approach too. In this approach, the target for drug action in the body is first characterized. For eg., the Cox 2 enzyme structure was studied in detail and a molecule, tailor-made to block the enzyme was synthesized. This approach was used for inventing Vioxx (rofecoxib).

Thus, there are two main approaches to create blockbusters:

a) screen natural and synthetic compounds, and extract or synthesize compounds on the basis of the natural template or synthetic molecule. Egs. penicillin range (from Penicillium notatum), cephalosporins (from a type of fungus), aspirin (willow tree extract), and fluoroquinolones (molecular modification of nalidixic acid).

b) the second approach is to synthesize molecules based on specific drug action targets.

These two approaches continue to be the mainstays of new drug discovery. Today, biotech methods and genomics are also used to create new drugs.

Billion dollar dreams

The pharma industry operates on the billion dollar dream. When a major pharma company launches a brand, the target is to generate minimum 1 billion dollar sales per year. A billion dollar brand is called a BLOCKBUSTER molecule or product. The first billion dollar baby was the 1977 drug TAGAMET (cimetidine). Glaxo followed up this molecule with its closely related molecule (called 'me-too' drugs, however, in India a me-too drug refers to the same generic with a different brand name, internationally, me-too drugs are molecular modifications of the innovator molecule) - ranitidine (Zinetac), which became another blockbuster.

The blockbuster approach has created around 100 blockbusters in the global pharma industry, with the famous Lipitor (atorvastatin) being the leading 12.2 billion USD blockbuster.

So the aim of pharma marketers is to have more and more blockbusters in the product basket. The below 1 billion USD drugs are not of high interest to most major pharma marketers. In fact, this is the reason that even though the global antibiotic market is 25 billion USD (Dec 2006), pharma biggies are not interested in this market. It is not easy to create blockbuster brands (above 1 billion USD sales per annum) in the antibiotic market (as it is not a chronic treatment market), and 60% of the antibiotics now are generic (out of patent) - hence pharma majors are not excited by this market.

The rising cost of new drugs discovery and high hurdle regulatory parameters make new product work riskier

If penicillin was discovered in the present age, probably it would not have made it to the market. The reason is adverse reactions. Same with chloramphenicol and streptomycin. Today, new drug discovery is costly and the high hurdle regulations make it more challenging, since failure rates are higher.

The tragedy of the blockbuster approach

The magnificent obsession of pharma marketers to have blockbusters in the product portfolio, has in a way created a tragedy for humanity:

a) certain disease areas are neglected due to low chances of creating blockbuster brands (eg., anti-infectives)
b) many below 1 billion USD molecules get ignored - for eg., if there is a promising drug for antilice activity, or as an anthelmintic, but if its market revenue potential is only 250 million USD or 500 million USD then the pharma company drops the new drug candidate from further commercialization work, as it does not fit the blockbuster (ie., 1 billion USD sales per annum) criteria.

As a result, IT IS POSSIBLE many promising molecules are lying neglected in the CHEMICAL LIBRARIES of pharma companies and other R & D institutions.

Hence, it is imperative that Google, Wikipedia, pharma companies, leading institutions, Govts., WHO, and other bodies come together to create an open source digital library of such chemicals. There is no point keeping the knowledge of these molecules (small and big molecules) buried in confidential files.

Wikipedia has heralded a new approach to knowledge empowerment. In fact, they are the perfect media along with Google to create an open source digital chemical library that provides all details of the molecule candidate (IUPAC name etc) and the status of the research & other research details related to it. Let us say, Pfizer has in its library a molecule with possible great benefits in Kala azar (a potentially fatal parasitic disease in North India) or onychomycosis (fungal infection of nail) - and Pfizer is obviously not interested in this molecule - it is best that all details of such molecules are put out on the internet through Wikipedia or Google, so that interested agencies can put the knowledge to good use. THIS IS THE CONCEPT OF THE GOOGLE WIKIPEDIA DIGITAL CHEMICAL LIBRARY. This will certainly create a new age in drug discovery or drug commercialization.

Today, pharma marketers are in the rat race to create blockbusters. The new product researchers are the Pied Pipers who are playing the musical tune promising great blockbusters - pharma marketers like rats fall for the tune, and may be even drown in the river of failure after experiencing commercialization failure or are unable to make the molecule a blockbuster. That is why you see the Pied Piper's image at the start of this blogpost.

Wikipedia and Google have made dramatic contributions to creating and sharing knowledge. In fact, they can even start courses and offer certificates, diplomas, and degrees! Let us say, Google and Wikipedia announce an online 'certificate course on nutrition'.

INTERESTED CANDIDATES SHOULD FIRST ENROL, AND AS PER THE COURSE GUIDELINES, LEARN AS MUCH AS POSSIBLE ABOUT NUTRITION USING GOOGLE AND WIKIPEDIA.

AFTER SAY 6 MONTHS, THE CANDIDATE SHOULD TAKE AN ONLINE TEST FROM WIKIPEDIA AND GOOGLE AND IF THE CANDIDATE PASSES THE TEST, BINGO! THE CANDIDATE CAN PRINT THE COURSE COMPLETION CERTIFICATE, FRAME IT, CITE IT IN HIS BIODATA ETC.

THROUGH THIS METHOD, WIKIPEDIA AND GOOGLE CAN CREATE NEW REVENUE STREAMS TOO IF THEY CHARGE FOR THE COURSE!!

NOW THAT IS FOOD FOR THOUGHT ISN'T IT?!


Any way, Wikipedia and Google are very important resources of humanity that can be harnessed to create open source digital chemical libraries (of magic bullets!) that can be mined for knowledge and create MODERN healthcare products for the benefit of humanity.

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