OSDD: A Journey Through Unchartered Waters

I will be stepping down from the post of Project Director, OSDD, upon completion of my deputation to Council of Scientific and Industrial Research (CSIR), on 31^st March 2014, and repatriating back to my cadre, Indian Revenue Service.

For those who are unaware of the background, a few lines. In India, civil servants are chosen at the entry level into specific services, and are trained in that area, They remain in those services (called cadres) for their career. However, government allows its officers to move to other departments for specific periods, on deputation. I belong to the Indian Revenue Service and I came to CSIR on deputation to lead the OSDD project as its project director. My period of deputation ends on 31^st March, 2014.

The warm welcome I got on my walking into CSIR on 6^th of August, 2008, did only increase overtime. During these five years I had the opportunity to interact closely with many brilliant minds in India and abroad, the leaders of science in India, and with the OSDD community and its committed members. It has been a rare honour.

Immediately upon joining CSIR, I had plunged into the pre launch activities of OSDD with two wonderful colleagues, Dr Anshu Bhardwaj and Dr Vinod Scaria, of course under the leadership of Prof S K Brahmachari who had conceived the idea and convinced the government to fund the program. Dr Anshu had joined even before me and had done lot of work. There was a small but highly committed team brought together by Prof Brahmachari comprising of: Dr Ramachandran, Dr Debasis Dash, Dr. Jyoti Yadav, Dr  Bhupesh Taneja, all scientists from IGIB, Dr Andrew Lynn from JNU and Dr Jajit Bhattacharya, an open source proponent and technocrat, then with Sun Microsystems. We all had one common intention, make OSDD a success and find new drugs for Tuberculosis (TB), which was identified as the first target disease. 

OSDD was launched on September 15, 2008 by the then Minister for Science and Technology, Mr Kapil Sibal. Mr Sibal in his speech referred to the 90-10, problem that 90% of the resources of the pharmaceutical industry goes to the diseases affecting 10%of the population of the world and stressed on the need to find new drugs for TB.  Prof Brahmachari fielded questions and exuded confidence. However, there was lot of skepticism in the air too. One senior pharmaceutical industry executive had laughed at the idea of OSDD and predicted it will never work.

It is now a global community of more than 8000 members from 130 countries. More than 100 institutions are collaborating on OSDD. At any point in time OSDD has about 100 PIs doing different projects. It is now a virtual drug discovery platform based on the open source principles.

The OSDD journey has been exciting at every step. It has all along been through unchartered waters. The initial skepticism has gone and OSDD is part of the global discussions on innovative ways of drug discovery as could be seen from the recommendation of the Expert Working Group and Consultative Expert Working Group of WHO. I am stepping down with the satisfaction that today, the scientific community recognizes OSDD as a serious effort, and the government of India and CSIR are committed to take it forward.

OSDD is now a fully functional translational, trans disciplinary, drug discovery platform.  Each of its component whether in biology, chemistry, medicinal chemistry is supported by strong teams from the community with robust underpinning of computational abilities in all these areas.

Our efforts in biology is to further the understanding of the pathogen and identify and validate novel targets. The systems biology approach is led by Prof Brahmachari, ably supported by Dr Anshu and several researchers. Dr Rajesh Gokhale and Dr Vinay Kumar Nandicoori at NII have been the early experimentalists on Mtb biology. Dr Inshad Ali Khan at CSIR-IIIM, Jammu, Dr Kishore Srivastava, Dr Sudhir K Sinha and Dr Sidharth Chopra at CSIR- CDRI, Lucknow, Dr Urmi Bajpai, Dr Sadhana Sharma both from Delhi University, Dr Niyaz Ahmed from University of Hyderabad, Dr Ashwan Kumar and Dr Pawan Gupta at CSIR IMTECH, Dr Ajay Kumar and Dr Sabu Thomas at RGIB, Trivandrum, Dr Umender Sharma at Gangagen, Dr Ritta Mathew at Bangalore and several others, whose names I have not listed but are significant contributors are adding value to OSDD every day. Prof Samir Brahmachari and Dr Swati Subodh leads the pharmacogenomics activities.

Our biological screening is handled by Ramesh Ummani at Hyderabad, Inshad Ali Khan at Jammu and Kishore Srivastava at Lucknow. Premas Biotech does the industry level screening of identified targets. All these activities are coordinated by Dr Geetha Rayasam ably supported by Dr Anuradha Kumar. 

OSDD has a strong chemistry team coordinated by Dr Haridas Rode. Our aim is to create a diversity oriented chemical library. There are about 90 PIs doing specialized synthesis ably led by Dr Chandrasekar at IICT. You may see the impressive list of lead PIs on the OSDD website http://www.osdd.net/collaborations/lead-pis/synthetic-chemistry OSDD’s medicinal chemistry efforts are led by Dr Bheemrao Ugarkar with his enormous industry experience and with a large community

http://www.osdd.net/collaborations/lead-pis/medicinal-chemistry

We have had the benefit of the leadership of Dr J C Yadav at Dr Ahmad Kamal and Dr Lakshmikantham at IICT, Dr Suresh Das and Dr K V Radhakrishnan at NIIST Trivandrum Dr Ramanna at NCL, Dr Sanjay Batra at CDRI, Dr Parminder Singh at IIIM Jammu and Dr Boruah at NEIST Jorhat. Dr Tushar Chakranorty initiated the academic collaborations. 

The industry partners in Chemistry are Jubilant Chemsys and Phytomyco. We also acquired compounds from commercial libraries. We are also working with GSK Tres Cantos facility.

OSDD’s development efforts are coordinated by Dr Sarala Balachandran. It has the benefit of advice of leaders like Dr N K Ganguli and Dr T S Jawahar. Almost who is who of the TB clinical research community has been associated with OSDD to provide their inputs and peer review. Dr Rohit Sarin, Dr Meyyanedu and Dr Saini at National Institute of Tuberculosis and Respiratory Diseases Delhi and Dr Soumya Swaminathan at TRC Chennai are leading the effort.   

It is a matter of pride to India that the clinical trial of a novel TB drug combination is being initiated on the World TB Day, 24 March, 2014. This novel combination of TB drugs is brought to India in collaboration with TB Alliance. This clinical trial is for MDR patients, who desperately need new drugs.  National Institute of Tuberculosis and Respiratory Diseases, a tertiary care hospital for TB patients, is the Investigator hospital. M/s G V K Biosciences is the Clinical Research Partner.  

OSDD has a strong informatics community coordinated by Dr Anshu Bhardwaj. OSDD's computational work is led from the front by Prof Brahmachari. Its bioinformatics community has all major leaders in the field from Dr G P S Raghava, Dr Vinod Scaria, Dr Ramachandran, Dr Debasis Dash, Dr Nagasuma Chandra, Dr Srinivasan at IISc, Dr Saudamini at NCBS, Dr Andrew Lynn at JNU and several others. There are several international collaborators including Sir Tom Blundell at Cambridge and Dr Kitano at Systems Biology International. The informatics group has engaged a large student research community through novel crowd sourcing efforts. M/s Infosys Ltd is an industry partner. CDAC has been helping with Garuda grid.

The Cheminformatics group include Dr Saurav Pal at NCL, Dr Narahara Sastri, Dr Anshu, Dr Karthikeyan, Dr Jaleel and others. Their international collaborators include Royal Society of Chemistry and renowned researchers like Dr David Wild. 

With the experience gained in working on TB, we have ventured to Malaria under the leadership of Dr Saman Habib who has put together a large team. Collaboration with Medicines for Malaria Venture is at an advanced stage.

On Leishmaniasis our efforts are led by Dr Shymal Roy at IICB. We hope to move into development phase of one of his compounds for Leishmania Donavani. Collaboration with DnDI is in place to take this program ahead.

OSDD’s community engagement efforts are supported by Dr Andrew Lynn, Dr U C A Jaleel and Vigyan Prasar, particularly, T V Venkateswaran.

Sir Dorabji Tata Trust grant has enabled OSDD to initiate Tata CSIR OSDD Research Fellowship. This unique fellowship supports large number of researchers working from home. There is a woman scientist component in  this fellowship which supports women working from home. OSDD thanks the support of Tata Trusts and Prof Jayakumar Menon for believing in it. More details about this one of its kind initiative at http://tcof.osddbengaluru.net/

The credit for bringing OSDD to where it is today goes to Prof S K Brahmachari, and to Dr T S Balganesh who moved out of a senior position in a multi national pharmaceutical company out of his sheer commitment to find new drugs for TB, and the core team. Above all, to the OSDD community!

No one would have imagined we would reach where we have reached. Working on OSDD has been a humbling experience. The commitment of the community members reminds of ones own inadequacies always made one strive to excel. At times at feel, OSDD could have gone much farther ahead but for my own limitations.

The strength of OSDD is its large research community, particularly the student community, for whom OSDD is an emotional enterprise. They are its driving force and I salute them.

I have always felt that Lord Alfred Tennyson’s poem Ulysses has special meaning. Ulysses, who after winning his battles and epic voyage returned to his Kingdom, but decided to abdicate his thrown in favor of his son Telemachus and start a new journey. In the poem Ulysses he gives his farewell speech and exclaims:

How dull it is to pause, to make an end,

To rust unburnish’d, not to shine in use!

He urges: ‘To follow knowledge like a sinking star, 

Beyond the utmost bound of human thought.…To strive, to seek, to find, and not to yield’.

OSDD is for those who seek to go beyond the ordinary!

It is time to pass the baton!

Adieu folks!

Satya Nadella and Some Thoughts on Governance!

One of the observations that struck me of the very interesting Satya Nadella interview serialized in various newspapers is:

“One of the things that drives me crazy is anyone who comes in from the outside and says, “This is how we used to do it”. Or if somebody who has been here for a while says, “This is how we do it”. Both of them are such dangerous traps. The question is how do we take all of that valuable stuff and apply it to create in the current context and raise standards.”

This is striking because of exactly opposite reasons of Nadella’s. Having worked in the government and knowing how it works, if there is one thing that can be considered a norm: anything that has been practiced and accepted overtime. You are always encouraged to do what has been done before, in the way it is used to. This has, in fact been institutionalized. When the government frames a new legislation, there are entire teams of draftsmen of the Ministry of Law to ensure that no new words other than what has been already used in some statute goes in the new one.

The way today’s governance is practiced and structured, anything that has been done before is kosher! To do anything new is tough. It calls for formidable persistence, management and other skills and an energy required to move a mountain!

Here is what a colleague at sufficiently senior level in the central government had recounted the other day. In a department which holds the vicarious responsibility of welfare of the working employees of the government, she tried to introduce something new- to celebrate ‘women’s day’. The question that was asked to her will not come as a surprise to anyone who know the government system – “Why should we do anything for the first time?” And this question came right from the top. Credit goes to this colleague who pushed it through. It is now being observed every year. Now the challenge will be to change this practice!

The Hindu gave a perceptive heading to report the Nadella interview: Finetuning has limits, it’s time to create. Satya says: “It is time for reinvention… future is not about our past success. It is going to be about whether we will invent things that are really going to drive our future”. Fine tuning has its limits!

This is the core problem of governance. Hierarchical, bureaucratic organisations are amenable only to finetuning. They are not designed to generate radical changes that will have impact on people’s lives. So governments could never be creative.

But there is a bright side to this inertia of governmental structures. Creative organisations are inherently unstable. The corollary is that non creative bureaucratic set ups are stable. As Nadella points out, mortality of a company is higher than that of a human being. There are few companies alive that are more than 100 year old. But governments have been running for centuries. Their non-creativity is their strength. This is why bureaucracy’s steel frame is the backbone of governments.

There is another bright side to this. Their staying power gives the confidence to private enterprise to flourish within the certainty of rules that they put in place. The legal system that does not use new words, that which is predictable, is exactly what private enterprises and bureaucracies want. They both do not like uncertainties. This may be a typical case of what the doctor ordered and the patient wanted being the same! 

This is where most often the politicians who head governments have to pay a price. Elected leaders in democracies have limited time and they have to face people again. People have aspirations. Unless they are creative and deliver on these aspirations, they will not get re-elected. The politicians, therefore has an unenviable task. They have to deliver through a system which is ‘built to last’, in essence through a non-creative system. Most of the anti- incumbency factors that throw out governments are the result of this.   

This gets exacerbated in the networked world. In the cyberworld everything is instantaneous and people are used to it. Everyone wants everything at the speed and ease of Google! This is brings in unprecedented challenges for the politicians who has to deal with a change resistant bureaucracy. They have to deal with people’s aspirations that call for providing services to the public through innovative organizations, which is not possible within governmental structures.

In todays India where 50% of the population is below 25 years who relate to the world through web interfaces of Facebook and the like, only way to meet this challenge is to make the government smart. The only way to make the governments smart is to convert all citizen interactions and service provisions through web interfaces. Otherwise citizens will never feel the smartness of the system. Removing human interface is the best way to root out corruption as well.

Having spent almost 25 years in the government, I have become a fan of the republican idea of limiting the role of government. Government should do what it is really good at: legislation, regulation and oversight. Governments will have a role in areas where market does not operate or provide incentives to private enterprise. Governments are good back offices. The rest should be left to innovative organisations that can ensure service delivery.

You may call me a neo liberal. I prefer being called names rather than be on the receiving side of an unresponsive bureaucracy!  

Public Funds: A Key Driver of Innovation

The column Schumpeter in The Economist is one that I read and like most for the insightful, razor sharp exposition of thinking and analysis. The latest one has the title ‘The Entrepreneurial State’. This article is based on a book, ‘The Entrepreneurial State: Debunking Public vs Private Sector Myths’ by Mariana Mazzucato of Sussex University. The book argues that the state (government) has played a central role in producing game changing breakthroughs and innovations.

The book demonstrates that unacknowledged state support has been the enabler of the consumer electronics revolution that has surrounded us. It lists a number of instances where state funding has been the source of many modern innovations such as Internet (which is rather known), HTML, and touchscreen (which have come from publicly funded universities) and even behind successful companies like Apple (which was funded by a government agency before it went public).

The most interesting part is that the most supportive of all nation states is found where one least expected, the United States. US government funds almost 60% of the basic research. Its armed forces pioneered the Internet, GPS and voice activated virtual assistants. They also provided much of the early funding for Silicon Valley. The research that produced Google’s search algorithm was funded by National Science Foundation.

Schumpeter argues that, at its best the state is the ultimate Schumpeterian innovator, unleashing the forces of creative destruction that provide strong tailwinds for private firms like Apple. To quote:

Economists have long recognised that the state has a role in promoting innovation. It can correct market failures by investing directly into public goods such as research, or by using the tax system to nudge businesses towards doing so. 

The above observation seems strange to many policy formulators in developing countries. Post liberalization, the effort in most developing countries, the neo-converts to liberal state philosophy has been acting what the neo-converts always do – go overboard to show your new approaches. Following this state investment has been moving out of many areas. Public research institutions have been asked to justify their existence in the liberalized economy. The neo-converts forget that businesses are short-termists and will innovate only where return on investment is assured in the near future. I hope Indian policy makers do read what successful and innovative states have done.   

Schumpeter argues that ‘putting all those different state funded technologies together into userfriendly iPads and iPhones required rare genius that deserve rare rewards’. True; but, for that there is the intellectual property system which ensures a limited monopoly in the market place. That should not obscure the importance of state funding which led to such technologies.

Pharmaceutical companies are bigger beneficiaries of state research than internet and electronic firms. Schumpeter says that behind most blockbuster drugs is the NIH support from its annual US$ 30 Mn fund. The following chart that Thomson Reuters had produced sometime back illustrates the point.

What is true for pharma is true in general is true for the rest of innovative enterprises. Most of the early stage innovations, which have long gestation periods and higher risks, are done in academic and not for profit research settings. It is in taking these innovations to the market that enterprises have their special skills. To be fair to pharma companies the development part is a long arduous and risky endeavor.

The lack of innovation in neglected diseases exemplifies this point. Pharma will show interest if there is foreseeable return on investment.  There has to be a market pull. Take the case of Tuberculosis, which even now treats patients with frontline drugs developed in the 1950’s and 60’s; prompting Nature to write an Editorial titled Orphan Giant. Global market for TB is estimated to be only about $300 million. Therefore there is no market pull. If we redraw the world map according to TB incidence the world looks different as below:

So, there is no economic or other compulsion acting either on the industry or the governments located far away from the countries where diseases are prevalent. Compounding this is the complex scientific challenges, unclear route to the market and regulatory environment surrounding the neglected diseases. A study conducted by London School of Economics about a decade back had revealed that big pharma is wary of taking development risks in neglected diseases.

The Open Source Drug Discovery (OSDD) programme, led by the Council of Scientific and Industrial Research (CSIR), India, had understood this dilemma of the market.  Therefore it advocates that public funding of research and development of drugs for neglected diseases. The countries that are affected by the neglected diseases have a responsibility to spur innovation by investing in research and development. India is showing an example on this through OSDD. OSDD has announced its intent to conduct clinical trials of an anti TB regimen by spending its own funds and at its own risk, in collaboration with TB Alliance.

Public funds need to support innovation. This is clear in the case of market failures. But what Ms. Mazzucato’s book reveals is that even behind successful market driven innovations, public funding has a major role to play. More than anyone else, the newly liberalized economies need to realize this. They just have to learn from the US.

Beware of the 'Good Idea Fairy'

The other day, I found my son engrossed in reading – ‘NoEasy Day’ by Mark Owen and borrowed it from him.  This book is a first hand account of the operation carried out by Navy Seals to take out Osama Bin Laden in his safe compound at Abbotabad in Pakistan. The book is interesting for more than one reason. Apart from being a page turner, written in gripping style and simple yet catchy language by the Navy Seal commander who actually led one of the teams which killed Laden, it contains a number of management principles.

The importance that US military attaches to training comes out clear from the book. Its personnel are put through some of the most excruciating and sophisticated training exercise that mimics the ground realities. They go to the field well trained, conduct operations, are called back to train again. The trainers are themselves people hot from the field. This back and forth continues and the Mark Owen comments that they themselves noticed that they have improved after such regular routines. But they also noticed that the enemy had also evolved with each of their postings. Each time you are prepared to face tougher challenges. The book gets its title from the Seal motto: ‘the only easy day was yesterday’.

One interesting concept that the Seals warn you to be on your guard is that of the ‘good idea fairy’. These are well intentioned people removed from execution of projects who come up with fantastic ideas for others to implement.  These well-intentioned people dream up solutions for non-existent concerns and slow teams down. 

Here is an example that is quoted in the book.  Laden was living in a neighborhood with lots of houses. During the operation there will be lot of gunfire and grenade blasts which is likely to wake the neighborhood up. Someone sitting far removed from operational logistics decided that during the middle of the night attack a group of Seals would be tasked with attaching a police light to the roof of one of Osama's Land Rovers in the early moments of the attack. A group of Seals were to push the Land Rover out of the compound to the road with flashing police lights to convince the locals that it is a mere police action. This group was to then join the battle.

This well intentioned armchair idea was ridiculous from an operational perspective. Why in the world would anyone going to catch the most notorious terrorist of the world, hiding in a compound abutting a Pak military base, without the knowledge of the country, waste any precious time in the attack. And, are the neighbors woken in the middle of the night by the sounds of war -- helicopters, machine guns, explosions -- next door would believe that a local police action was taking place, simply because a car with a flashing blue light happened to be blocking the street? The idea was discarded by the guys who were well trained and experienced in carrying out raids in Afghanistan and Iraq.

The origin of the term ‘good idea fairy’ is in the U.S. military and describes a mythical creature that whispers advice and ideas into the ears of leadership, causing hundreds of unnecessary changes and countless wasted man-hours. Owen says in the book: “if we had all the time we wasted fighting the good idea fairy back, we might have gained few years of our life.”

We all come up against good idea fairies at different points of time.There is a blog by a school teacher how the theory is applicable even in everyday work and on how one should be careful.

There is another interesting blog on good idea fairy at EngineerLeader cautioning against this fairy who shows up in the eleventh hour just when the moment of execution is about to arrive and brings in a whole list of unnecessary changes and additional work. Engineer Leader points out that it is the leaders responsibility to control the good idea fairy and the only way to do it is through courage and preparation.

The good idea fairy preys on the inexperienced, easily confused, and leaders unable to listen to sound advice. To keep the fairy away the engineer leader suggest the following:

Surround Yourself with Subject Matter Experts:  It is not possible for a leader to know everything, nor should you.  When you’re handed a project to lead and you don’t know how to solve each minute component, it is the leaders job to find those that do and enlist their support.

Listen to Good Advice.  Everybody has an opinion but few have good advice.  A good leader develops the intuition to tell the difference, and actually listens to it.  The leader should listen to everyone’s input but then make the decision on the good advice. 

Prepare well and eliminate confusion: Good idea fairy is more likely to visit the confused ones. To eliminate the confusion in problem solving, first step is to define the problem correctly and then begin investing time towards solving that problem.

 Set a Good Idea Fairy Cut-off Date: Ideas are good to have.  Do proper planning through brainstorming.  Get the stakeholders involved and it may lead to innovative and smart solutions. Ensuring that everyone has a chance to contribute their ideas can go a long way to check the good idea fairy. However, at some point the ideas aren’t helpful anymore, and a cut off date for new ideas need to be set. 

The management principle to be learnt: One important management principle that comes out of No Easy Day is that you need to trust the operational leadership. The best laid plans are the first casualty of the battle. So, many a times the best plans are simple and flexible. The operational leadership on the ground should have the flexibility to execute and innovate on the go, especially in complex, constantly shifting, unpredictable situations. It is easy to suggest new ideas, but the one on the ground, executing the task knows how best to handle a situation and it is better to leave it to them than to rely on 'arm chair quarter backs' who might not even have played the game, except watching TV, and are full of ideas and suggestions on what the team should do. 

Keeping the good idea fairies away is a leadership challenge.