By Nithyanand Rao, Aroon Narayanan, Rohan Karkhanis and Arjun KG
Prof. S. K. Brahmachari, the former Director-General of the Council of Scientific and Industrial Research (CSIR) was here on campus for an EML on 28th January. Among his many initiatives as DG-CSIR, was the Open-Source Drug Discovery model, for research and development of drugs targeting diseases which are often overlooked by the giant multinational pharma companies. T5E had a chat with him on this, and more.
At the Indian Institute of Science, where you did your Ph.D., you were mentored by such illustrious scientists as Dr. G. N. Ramachandran. Any particular memories?
Oh yes. G. N. Ramachandran was someone everybody was scared of. He had moved from Chennai to Chicago to Bangalore. In 1974, I was a PhD student. G. N. Ramachandran’s first project was from CSIR. I became his JRF in a project, and I didn’t have a First Class — I had 59.7% or something, so I was a little short. I thought that you had to impress GNR, or you would not get a Ph.D. registration.
Prof. Ramachandran would go to lunch at 12:30. I would sit right opposite to his room, so that he could see me, see that I was studying. Then he’d come back at sharp 2 o’clock. So I’d run to eat lunch after he goes and I’d come back before he returns, and start reading. So GNR comes back, and he’s very happy to find that I am still reading. He was a very childlike person. He would ask me, “You had your lunch?” I’d say yes. But then he sees that you’re there in the room before he goes and also when he comes back. And that’s how I impressed him. I think it had a very strong influence on my early scientific career, meeting a tall person like GNR.
Coming to the present day, new regulations introduced in 2009 permit researchers at government-funded institutions to hold equity stakes in scientific enterprises and spinoff companies. The new rules also permit research institutes to hold equity stakes in commercial enterprises. What impact has this had on the research landscape in India?
All our good students who wish to become scientists, they all go abroad, and it’s very difficult to bring them back. One of the reasons they don’t want to come back, is money. Now, the Government of India cannot pay more than a certain amount of money. So the idea was that if we empower the scientists to have an equity, to have a spinoff, they could make money. Number two, we also create an entrepreneurial spirit and it will create jobs. With these ideas in mind, I had to go through a large number of departments when I was the DG-CSIR. And it was notified in 2009. Since then two companies have been spun-off and several more are in the process.
I think Indian scientists are hesitant to take risks. I think general entrepreneurial energy in scholarly individuals in this country is a little low, unlike the Western world. Otherwise, we should have had many more people applying. But I can see this increasing. Now other institutions have taken this up; other institutes are also following. It’s not CSIR alone. It’s an all-India approval.
So would you say that it has had the expected impact?
It has at least had the psychological impact, that if I want to be rich, I can be rich. I can see that the younger breed have started now. Our target is that five companies per year should come out of CSIR. Twenty or thirty per year across the country. You can’t expect more than that; I do not expect more than that.
You say in one of your interviews that the potential growth in informatics has not been exploited as much as it could have been by the large industries. Do you think private companies in India, both in the IT and the biotech sectors, could be doing more to support research and development?
Today, I think TCS is the only company which has taken advantage of the bioinformatics opportunity and potential, and has a substantial — I think 300 million dollars per annum — business. But it’s still a service business, not a discovery business. Our IT companies could have made discoveries with their cash reserves. We could have provided the world with various novel software in healthcare. We cannot say that, except Tally, there is something that is Indian. Tomorrow if Infosys is dissolved, what wealth will be there? Nothing. Tata has done better. So the hardware industries with lots of limitations — Tata, Birla, Reliance — have done better than IT could’ve done with its huge potential. See, in medical informatics, medical imaging, we’ve completely failed. We’ve become a supplier, a service provider.
I shout at the top of my voice in all the FICCI and CII meetings. But nobody picked it up. If we had, we could’ve been world leaders in medical informatics. Even today there are new opportunities; for example, this big data science. So maybe we can make a difference. The companies with lots of cash reserve, instead of giving away a lot of dividends, they could’ve taken 10% of their dividends and invested in the future. They would not have looked back and worried about their balance sheets. Today they are worrying about their balance sheets, many of them.
We have not been able to create a company like Google. Why was Facebook or Twitter not created in India? It could’ve been done by any of these companies that created so much wealth. Just like the way Reliance decided to put 1000 crores for oil exploration, the way Reliance has gone about making 4G applications, some of these companies could’ve easily decided that we want to become the medical informatics leader in the world, instead of just supplying or writing software for GE. Sixty percent of software of all medical instrumentation is written by Indians. But somebody told them what to make. Our problem is, we neither created young people who know what to make, nor trained them by telling them what to make. How to make, we know. What to make, we don’t know. So we need somebody else to tell us what to do, and that is my disappointment with software companies. You look at the Open Source Drug Discovery (OSDD) project — that is my answer to the software guys. You see, here is one example where we decided what to make and the world follows. I thank Narayan Murthy because he came and supported us. I wish we had dozens of those examples I could’ve given as a proud Indian; but we don’t have.
What further measures are being considered by the CSIR and other government organizations do to promote cooperation between the public and private sectors?
See, in this OSDD, we have at least 15 CROs — corporate research organizations — which are participating. Unfortunately in the last two years, private-public partnership has become a dirty word because of so many scams, so many confusions, and thereby an apprehension has been created. So although there have been instruments created, there is a general hesitation because everybody is scared what would be found fault with.
Secondly, it is also because of economic reasons. Today, industrial growth is low. When industry growth is low, they don’t invest money, in order to survive. But the thing is, it is when the industry growth is low, that you should invest in R & D, so that you can come out of it. And this is the contradiction Indian industry has gone through and is going through.
About the Open Source Drug Discovery (OSDD) initiative — what progress has been made so far in developing drugs for TB?
When we started in 2008, we realized that there is no investment for something like tuberculosis. For 47 years, there has been no new drug. Should we accept this or should we try to make a change? The idea was, can we involve young people in the drug discovery process? The entire development of IT has taken place with the young people, whereas in drug discovery young people are kept out. If you look at it, people in the age group of 20–35 are not there in pharma companies. And whatever they do, they do like technicians — codified screening, codified assay. They’re not involved in thinking. Today in the entire IT industry, everything is done by people between 22 and 35. So I thought, can we use people from this age group to try discover drugs for diseases where there is no investment, whether we can do as a collective, open source?
The reason for open source is that we don’t have to bring lawyers into the picture. There would have been lots of problems with credit sharing, intellectual property, who owns what, etc. So we needed a portal where everything is stamped, everybody gets credit, where micro-attribution is possible. For the proof of concept, we started with a thousand people. In the first year, we got about 900 odd people, and today we have over 8000 people on the portal from 100 odd countries. At any given time, 20% of them are active. Now, we started with a few projects, and today we’re having over 250 and, we have 180 principal investigators including some from abroad.
Our idea was that, first, we want to build a model of the organism; which we have done. The second thing we were supposed to do was identify the targets, which also we did. Then to get the molecules which would target the target. This also we have done. Then the idea was to take the molecules to the clinical trials. We knew that it will not be possible to do everything by ourselves from the beginning to end. So we sourced people and asked everybody to come in. We were lucky. We are very glad to say that people believed in the open-source philosophy. Even the TB Alliance has joined, which is partially funded by Bill Gates.
Our aim was to take one molecule combination to the clinical trial stage. So, as far as I’m concerned, this was my target for December 2013. So I’m done, 100% achieved. In a time frame of five years, that’s the maximum we could have achieved. We have taken up a new project, with drug development, disease diagnostics and drug delivery — all OSDD. So that’s a new, large project.
So has the TB drug reached the stage of clinical trials?
Yes. The first combination molecule has been cleared by DCGI (Drug Controller General of India) for clinical trials. We have got all regulatory authority clearance, and the patient recruitment starts — Chennai will also get participants. That’s the idea.
You were instrumental in the creation of the Academy of Scientific and Innovative Research (AcSIR), promoting interdisciplinary research in CSIR labs. Could you share with us the impact this has had so far?
I realized that a million students graduate every year as B. Techs, mostly from private institutions. But when I want to recruit a young engineer as a scientist, there’s hardly anyone with a Ph.D. Because these days you get a B. Tech, you get salaries, jobs, you don’t worry about anything. You get an M. Tech, you get your job. You don’t worry about Ph.D. It’s too boring and long, and the fellowships are not commensurate with the market value. So the idea was, 960,000 students are becoming engineers every year. Isn’t it true that one percent of them are becoming engineers by mistake, that they never wanted to become engineers. Their parents pushed them; they really wanted to become scientists.
So, we started with the post graduate diploma programme in engineering by announcing that we are looking for bright students who will be, if they’re successful, absorbed for Ph.D., and later for jobs. We realized that if we’re successful, we could attract so many bright students. And you’ll be surprised that we had 26,000 applicants with a CGPA of 7 and above, who are interested in doing an M. Tech-Ph.D. programme. We selected only 120, and they were all 8+ CGPA. Then they had to work through the entire 64-credit course program. The courses people do in the engineering colleges are very boring. They do the same projects. But here in CSIR laboratories, they can do real-time projects, such as working on the GSLV mission. Actual real-time, real-world projects that they are doing hands-on.
To my surprise — we have the fourth batch now, I addressed the fourth batch recently — nobody wants to go out. Not a single person wants to go abroad. We only reject them if they don’t get a CGPA of 8 all along. 10% of them are screened out, 10% don’t make it, and another 10%, even if they’ve got 8 CGPA, we screen them out because while they may have got the score, they haven’t done anything good in practical matters. Or they have an interpersonal relationship problem, they cannot work together well. So whomever we are retaining, 70–80 or whatever it is, nobody wants to go out. So this is one way of creating a large number of Ph.Ds in engineering, which is absolutely in short supply in the market. They are doing a Ph.D. in real-time problems, not some theoretical problem. Of course, for a science Ph.D., they used to get registered in some university, and there was a complete lack of standard. Now there’s a uniform standard, uniform coursework. A lot more interdisciplinary projects between laboratories. So this is a virtual meta-university of AcSIR.
This is just the beginning, instituted by a 2012 Act of the Parliament, so I’m sure it will take five more years to mature fully. That is something I’m personally interested in, because AcSIR has given me an academic professorship, which lifelong, along with 4 others. Therefore, I have a commitment. I’m sure I shall be able to do that sincerely. Personally, I believe the students are very good. They get new opportunities that weren’t there before. Because there are huge resources — equipments and machines — and interdisciplinary problems, because there are so many CSIR laboratories, you can use one or the other to solve real problems. Earlier, the problem used to be solved by one discipline. Today, this is not the case.
You talked about students not wanting to go abroad. There is also a scheme wherein senior Indian scientists who are working abroad, are encouraged to come back to India. Could you tell us about this scheme?
We wanted to bring back scientists and technologists of Indian origin (STIO). But when we bring them from abroad to senior positions here, they might find it difficult administratively, managing indian processes, rules, positions. But one thing I observed is that the trend has changed now. Earlier, nobody wanted to come back from abroad. Now people want to come back permanently to India. That change has taken place.
Unfortunately, the very best Indian scientists who are abroad are very busy there. One of the last proposals I gave before I stepped down as DG-CSIR, was to consider people of international origin. There are lots of people from Italy, Greece and Spain who are very good and who are really interested in coming to India. Maybe we should internationalize our scientific community by 5 percent. This would give us a new vigour.
I find another interesting thing — while I thought that this scheme of bringing Indian scientists back will make people very excited, actually people are a little nervous to bring very competent people within the system. They fear that they will lose their position and respect. So, there’s a certain amount of human psychology that has inhibited the full utilization of the scheme. Now the DST has announced a very good scheme wherein they will give a 100,000 dollars annually — and that’s big, far higher than my scheme.
You have demitted office after six years as Director-General of CSIR. What part of your career would you say was the most satisfying? What has given you the most satisfaction?
You know, I’ve played three innings. First as a faculty at IISc. I spent 23 years at Bangalore, at IISc, of which a part was as a Ph.D. student, and then as a lecturer and professor. That was the most satisfying intellectually. Then in the second phase, I came to CSIR at Delhi, to build the genomics institute. So I built the Institute of Genomics and Integrative Biology (IGIB) — that’s ten years back. And the third phase I played was being the DG-CSIR, for 6 years. If you ask me which is the most satisfying, lasting contribution of mine, it is building the Institute of Genomics and Integrative Biology. The idea I had was that I wanted to bring genomic science to India, bioinformatics in India, to build and be seen by the world.
Part of your work there involved the Indian Genome Variation Project…
Yes, so the Indian Genome Variation Project was with a very limited fund. We could do something large which the world could then notice — to map the disease genes in the population of India. Today, what is satisfying is not only that we have the Institute of Genomics, we have so many companies, so many entities which are working in genomics. We can see now the potential applications of genomics in health care. India is no way behind anybody else. Still, we have a shortage of entrepreneurs, but as far as knowledge base is concerned, we are there.
It’s one field of science where I can see that from a single individual effort, there has followed collective growth. So that’s very satisfying, to see that what you have created, has proliferated. And today we are a dominant force, without spending hundreds of millions of dollars. I go everywhere in the world and I’m very pleased to see that always I find one student of ours, whether it’s Asia or it’s all the way to the Arctic, who will say, “Sir, I was your student or I was in your IGIB.” Or now of course, in OSDD, where he can participate. I think that’s very satisfying, when you see those young people there.
OSDD has found quite a few detractors and skeptics internationally, with articles being published in Nature and The Hindu a few years ago questioning the scale of its impact. Your take on this.
You know, we as Indians, why we can’t beat China? Because we have this “crab syndrome”. You know that story, a container of crab was sent by ship. Somebody said, how come we have not covered it. The other guy says there is nothing to worry, because if one crab wants to come out, the other crab will pull it down. They’re Indian crabs, so they will never get out.
Now, I think we lack confidence as a nation, that we can do anything new that the West hasn’t done. Even here in IIT, you IIT students tend to think that if it’s not done by somebody abroad, how can it be done by someone here sitting in IIT? That’s why IIT is not MIT, correct? So I know people will criticize, people will say things. Of course there are also other interests, vested multinational companies’ interest. I knew that among the Pfizers of the world, this was a point of concern — how is open source working? Some people like to write, it gets good publicity and whole papers are published about this. The fact remains that for any scientific work, it takes a year or a year and a half to get to publication. It doesn’t happen overnight. If one goes back, when was the human genome announced?
June 2000. When was the finished genome published? 2003. The first draft was done in 2001 and the final draft in 2003. We also published in 2011 and 2012. All these papers are now published, several of them in peer-reviewed journals. So I don’t think I need to answer. That’s the way it is. Therefore, what I learnt is that you have to be very strong mentally. And I have no problem; I actually enjoy it if people are critical about me. The more the wind against you, the higher you fly. So OSDD has actually flown higher because the wind was strong. I actually thank them for being critical.
Other than TB, what other diseases are being targeted by OSDD?
In my life, I can do only one. But now there are three or four scientists, mostly women — who have taken the lead on malaria. However, irrespective of funds, I have one desire — to use the open-innovation model to find a low-cost, out-of-patent cancer drug, repositioning it with combination therapy, for the really poor people. Because cancer is too expensive for treatment. And people are only prescribing the latest, most expensive drugs. I believe we should be able to create, for some cancers, out-of-patent or older cancer drugs. There are over a 100 cancer drugs approved by the FDA over the last 40 years.
Finally, any words of advice to students of IIT Madras? Any message that you would want to convey?
Please remember, India is still a poor country. You all are very privileged that our country has created institutions like this. You have something to pay back. And I think the time has come when students of IITs must dedicate a part of their time to pay back to the society, and not worry only about their own growth, their own achievements and their own aspirations. I’m not saying that this means you sacrifice everything. If you have wealth, share it. Let there be a part of your heart where you constantly worry about the unfortunate 800 million Indians who can be taken out of their poverty and problems and troubles only by you. The best of India has to lift them out. I feel that if students of the IITs believe that they can make a difference, they will make a difference. And India desperately needs it.