I recently had the opportunity to speak with Dr. Samir Brahmachari, the new Director General of CSIR. It was a pleasure to see the enthusiasm with which he spoke about his open source drug discovery model and his plans for the growth of CSIR. Given all the media attention that his OSDD has already received, I thought it would be best to dig a little deeper into the model. We provide not just excerpts from his interview, but also excerpts from his presentation on OSDD that he was kind enough share with us.
It was fortuitous that while I spoke to Dr. Brahmachari, other scientists and physicians were present. This gave me a chance to be party to the discussions between great minds and witness the concerns they all very clearly share for issues ranging from drug quality to affordability and pharmaceutical marketing tactics (remember our posts on Competition law?). Here are some of the excerpts:
Question: Congratulations at being appointed DG. I am sure it is an opportunity as well as challenge. How do you feel?
Answer: I’ve been given a job, entrusted with a responsibility and confidence of the Government. I have to execute the job and am happy to do it. In the 65 year history of CSIR, all leaders have taken responsibility and done the best that they could do what they thought to be appropriate for the country and the CSIR at that juncture. My job is to do the best that I can in this juncture of time, when India has opened up. My job is to keep CSIR relevant and progressive in the new environment, in the new resurgent India.
Question: Everyone is excited about your open source drug discovery model. Yet, there are some concerns that it may not be practical. We hope through this interview to address some of these concerns. Could you please elaborate upon the OS model and CSIRs IPR strategy?
Answer: Open Source is a passion of mine, and it is part of a larger IP strategy for CSIR. We at CSIR hope to use Open Source for two different projects which I will roughly divide for purposes of explanation into (a) Open Source in Pharmacogenomics and (b) Open Source in drug discovery for infectious diseases (especially TB). The latter has already been covered extensively in the media. I will touch upon that and discuss the pharmacogenomics model in more detail.
We need first to understand the background, which is true particularly for India and other developing countries. The need is to make drugs at low cost. In an environment where implementing subsidies and controls may not always be easy, it is best to discover/invent drugs at a low cost. In order to do this, we need to cut costs. For example, we don’t want to pay money to lawyers (Laughing)– I feel that [in protecting inventions] the lawyers make the most amount of money; for patenting, transactions, protection – in each aspect, we are paying the lawyers and this is one of the reasons why the costs go up.
In the open source model, we will just put the entire drug discovery process under a click wrap agreement [similar to the GNU GPL?] – yes, with appropriate modifications. And since we will follow a not for profit model, lawyers will work for us pro bono.
Question: Does this mean that the current CSIR strategy of focusing on patents is now going to change under your leadership?
Answer: No. Patenting will continue. Patenting is also a strategy. Patenting is a strategy of a business – we don’t make bombs to drop bombs, we make ammunition as a defense to prevent others from attacking. Our patenting strategy will also be for this purpose.
Further, we never see a wall around a paddy field, but there is always a wall around a factory. This is not to say that paddy is worth less than a factory or that we need not protect the paddy field. However, we need to distinguish between the type of protection that is practical and affordable in the light of the demand and in the light of what the consumers who demand it can afford to pay. Paddy is something that is required even by the poorest of the poor. But if we build expensive walls around the paddy field and pay money not only to build the walls but also maintain them, it will only hike up the price of the paddy, and make it unaffordable for the poor. We therefore protect the paddy by putting up a scarecrow. A scarecrow would be like an open source license. Around a factory, which produces goods that cost more to produce and can be priced higher because consumers are willing to pay more, we build and maintain walls. These are patents.
Similarly, in the case of inventions, we will not put a wall around drugs that are required by the masses and which we want to sell for cheap (such as Hepatitis or TB drugs), but will put a wall around drugs that have high market affordability, where the diseases that these drugs treat are not yet prevalent among lower income groups. In addition, by patenting, we can also challenge monopolies.
Thus, in growing paddy, we will use an open source model. While building a factory, we will patent. If my discovery benefits millions, and I want to give it to them for cheap, I do not want to raise the costs by spending a lot of money in protecting. But if the R & D is highly expensive, then we will patent.
Question: If CSIR doesn’t patent its inventions, why will the industry want to take a license and invest in bringing the drug to the market?
Answer: Why do generics bring a drug to the market? They don’t have a patent. For OSDD for TB, we want to make the first molecule itself generic. Further, we don’t know how to discover a molecule, so we will use the world’s brain to discover the molecule. In this way, we will also learn how to discover a new molecule – open source! Just like the cost of cell phones came down after competitors came into the market, we want to make the first molecule generic and have low cost right from the start.
Question: Drugs are different from cell phones. Drugs are ingested by people; what is the strategy for costs involved in clinical trials?
Answer: Clinical trials will be conducted by the companies interested in marketing the drugs.
Question: What would be the incentive for first company taking the license to go through all the expenses of a clinical trial only to give others the second mover advantage?
Answer: Exactly… Here, the government will subsidize clinical trials. The government will pay, for example, 50% of the cost of clinical trials. The rest of the cost may be shared, say by 5 companies. Simple economics: Risk to reward ratio. The companies will take 1/10th the risk and will get 1/5th the reward.
Question: In what other ways will you use the open source model? How soon can we expect to see results? I am sure our readers would love to know hear details about your OS model in pharmacogenomics.
Answer: Making new drugs is one issue. What we need to realize is that there are issues more pressing that creating new patentable drugs. There are enough and more drugs already in the market. The issue that we are facing is promotional pressures often leading to the ouster of existing drugs from the market on the grounds that the newer drug has fewer side effects. Undoubtedly, next generation drugs might have fewer side effects for some people. But the large majority do not suffer any side effects even from the first draft of the drug. (For example Metformin for Diabetes, Phenytoin for epilepsy) Why should they have to pay more for a 2nd draft, especially when they cannot afford it? Moreover, it is only in the long run that we will know what additional side effects the newer versions of drugs will have. For many disorders/diseases, long term or even life long treatment is necessary. Short term clinical trials for drugs for such diseases might not reveal all long term side effects.
Lets take an example: To treat epilepsy, we have Phenytoin, which is a 1960s drug that is off patent and Big Pharma is not interested in it. About 5-7% of the population may have side effects to this drug. So pharma companies come up with the next “draft” of the drug. Phenytoin costs Rs. 800 for the whole year. The next generation drug will cost Rs. 11,000 for the whole year. How many can afford to pay Rs. 10,000 more for this drug? That too, just to avoid some side effects that affect only a small % of the population? I might not even fall into this 5-7%. Why should I pay Rs. 10,000 more? At the same time, we need to make sure that those who have serious side effects, are given the newer version of the drug. To make the distinction, we use pharmacogenomics and OS.
Question: Could you please elaborate on this model?
Answer: We can do pharmacogenomics, identify the people who have side effect and keep the low cost drug in the market. By analyzing blood samples, I can know whether or not an individual will have any side effects to a drug. For pharmacogenomics, with the help of OS, we will: [From OSDD presentation:]
1)Decipher the genomic basis of variability in drug response.
2)Provide the molecular rationale for safe usage of low cost drugs in Public Healthcare system (eg: Epilepsy, Mental disorders etc)
3) Provide “right dosage of right drug to the right patient keep
4) Avoid adverse events to commonly used therapeutics
and thereby, keep low-cost drugs/orphan drugs in the market by promoting their safe and effective usage!
By analyzing your blood cell DNA, I can tell you that this drug will not have side effects for you because you have XYZ biomarker. How can this be done? We will analyse 100s of people who have side effects and find, say, a common variation in the genome. This variation could be a systematic mutation in the receptor. So we will know that this mutation in the receptor is associated with the side effect. Once we know this, we can do a one time test, determine whether or not a patient has this mutation. If not, she can take the low cost generic drug for life without any fear. Further, we will develop this test using the open source model so that the test is also available for cheap.
Question: What about cases where one drug might has multiple side effects?
Answer: Drugs like Phenytoin have been in the market for many years. We are aware of the type of side effects that exist. Making tests for these known side effects is therefore possible. When a new drug comes into the market, we do not know the types of side effects that may arise because we do not have any experience with the drug. With the old drug, we have the benefit of long years of experience. We can therefore work better with the old drugs in creating tests and ensuring that these drugs continue to stay in the market. Therefore, for such drugs, we use OS and give the right dosage of the right drug to the right person. Here we don’t use OS to discover new drugs, we provide the diagnostic markers for free so that everyone who has no side effects can continue to benefit from the old cheaper drugs.
In a large majority of people, older drugs work very well. Only a small % of people will have problems (side effects). If these problems are addressed using OS, we can keep low cost drugs in the market.
Unfortunately, today, the problem usually arises not because of differential toxicity but because of differential pressures on sale: Pressure by the companies marketing the drug, and unfortunately in some cases, even by mis-informed doctors just to get the new drug into the market and push the old drug out!
The OS model in Pharmacogenomics can work beautifully by providing diagnostic markers for free. [Q: Who will be the contributors to this model?] A: Anyone!
Question: Absence of a considerable market (in terms of monetary gains and recouping R&D expenses) is one of the reasons why there has been little interest shown in developing drugs for the “poor man’s disease.” Can you please elaborate on how you the OS drug discovery model can help overcome this situation?
Answer: We need a multifarious approach for this. But first let us look at why we need an OSDD model. Consider this: What % of the entire world’s business earnings are spent on health care? Peanuts! Yet, health is fundamental right. We are violating the undertaking of “Health for all”. In protecting IPRs, we are not protecting health. We are protecting the investors. While there is no harm in doing this when we are dealing with the rich man’s diseases, we need to change the attitude and approach towards drug discovery for the poor man’s disease.
Another point to consider: America is the country that has made all the discoveries, holds all the patents, has won most of the Nobel prizes, and yet its people are paying >100 times more for drugs in their own country! Why? When the US faced the threat of SARS, it decided to get generic drugs from and immediately, MNCs droped their prices from $5 to 96 cents. 80% of money market for pharmaceuticals is America and Japan, yet, 46 million Americans stand on the border of Canada to get Indian drugs. Indians themselves carry all their personal drug requirements from India if they plan to travel overseas. These questions are important not only for developing countries, but also for the developed countries. Why are the people there agreeing to pay more and more?
Yet another point to note: Today, there are 399 drugs in clinical trials for cancer and only 6 in clinical trials for TB. Yet, look at the % of people that die from cancer v. TB. [Question: But for TB there are effective drugs, for cancer, there are no effective drugs]. There are no effective drugs for latent TB. Further, till today, more people die from TB than from cancer. Yet, the available medicine is a 6-9 month medicine which is very toxic. We want to use all the information that we have on TB – the disease, host-pathogen interaction, drug interactions, drug reactions, knowledge available in the literature, in patents that can help in target discovery with the help of in silico systems biology. This will reduce time and cost of drug discovery.
We need also to create an innovation and R&D mind frame amongst our students; starting at home, at early schooling, college and university. Our OS model will help introduce this type of thinking in the colleges and universities by giving students a practical platform to contribute in. In the OSDD model, we will also provide incentives in form of recognitions and what we call “Microattribution” – a novel credit system for contributors. As a society and as a people, we need to understand that “so much can be achieved in this world if no one cares who gets the credit.”
HIGHLIGHTS: (From Dr. Brahmachari’s presentation on OSDD)
Why Open Source Drug discovery?
1)“Drug Discovery” is not easily reproducible.
2)Drug Discovery needs to move out of closed doors of Pharma Companies to the open sky for the younger generation to participate globally.
3)Present IT infrastructure, connectivity and high throughput analysis capabilities make OSDD possible.
4)The work can be done by Academia, University students and CRO’s at much lower cost.
5)The aim is to make the NCE generic as soon as it is discovered.
What are the objectives?
1) To establish a novel Open Source platform both computational and Experimental to make cost effective drug discovery for infectious diseases possible, thereby making high social importance drugs affordable for masses in developing countries such as India.
2) To create a “Team India Consortium” approach with world wide participation and international collaboration
3) As a first phase, drug discovery for M.tuberculosis including drugs for drug resistant and latent tuberculosis will be undertaken.
4) A novel comprehensive System Biology approach will be undertaken for broad spectrum antibiotics.
5) In Phase II, other infectious disease drug target like Malaria, HIV will be undertaken.
6) International collaborative efforts will be undertaken through national, international and philanthropic funding.