Padma Shri Prof. K.N. Ganesh sits for a Questionnaire!

Krishnarajanagar Nagappa Ganesh, is an extremely influential character in the field of science and research, especially as a bio-organic chemist. Winning several awards and plenty of recognition throughout his career, he has been the founding director of IISER Pune (2006-2017) as well as IISER Tirupati (2017-2023). He is widely known for his work in the chemistry and biology of nucleic acids, DNA technology, and structural biology of collagen peptides. Dr. K N Ganesh was a recipient of the Padma Shri award in 2023 and the Shanti Swarup Bhatnagar Prize for Science and Technology in Chemical Science.

One of our editors had the opportunity to meet him during his internship at JNCASR Bangalore, and he (along with our team) was thrilled to have an opportunity to interview him and gain some very profound insights into his life, career, academic trajectory, and more. We could not be more honoured and excited to present to you the following article:

So, my first question is one that you might have been tired of getting asked of. Even at this age, you come here to JNCASR regularly. Before this, you were the founding director of IISER Pune, and then, you founded IISER Tirupati. What motivates you to come over here in the first place at this age, having achieved everything you had to? In fact, you even won the Padma Shri a few years ago, so it makes me curious.

“See, science is one area where whatever you do, you do it for your satisfaction. Of course, there are a lot of benefits that others get, but in any other area, by working in that field, you are making someone else rich. You are working towards someone else’s idea. However, science is one area where we do things for our enjoyment and fulfilment. If I do something out of passion, something I enjoy, I can continue doing it for the rest of my life. Even if I can no longer perform experiments, just thinking about it pleasures me. So, science is, in that way, a unique area where you do something you are passionate about, and somebody else willingly funds it through research projects and other ventures.

Somebody gives you money to try your own idea in no other aspects of life, right? I mean, they will get rich from your idea. Science is the only one that enriches you; it gives you something: satisfaction. In the initial days, you want to do something you have been trained to do. For example, at NCL, as you mentioned, I was trained in organic chemistry. I thought organic chemistry and nucleic acids were essential because nucleic acid, DNA, and proteins were not considered chemicals. Organic chemists would say it was all biology. But we know they are molecules; they are chemicals. So, I started working in that area. I could do whatever I was trained in, such as synthesis, applications, etc.

The important thing in science is to ask questions. Every time you complete something, it should not become a 10-year project. It should lead you to another question, then another, and another. That is how science progresses. For example, I did something in DNA, then moved on to other things as new questions arose. It is all about self-directed inquiry. However, you initially choose problems you can solve using your existing techniques. We never worry about how significant the problem is at first. After doing that, people will recognize your strengths.

Then, you move to the next step, asking questions beyond your competency. You become more mature and think, "Okay, I have learned and done these things. It is good. But what is worth doing?" You must move away from your initial comfort zone. That is how you start your independent research. For example, Dr. Govindaraju was my student. He did DNA synthesis but is now doing entirely different things. He acquired that capability after doing some research and asking new questions.

As you get exposed to more science, something will interest you. You are limited only by the fact that your abilities should not stop you from asking new questions. When you ask new questions, you forget about your current abilities. Ask questions that are worth solving and interesting. Then you say, "Okay, this is a question, but how do I find an answer?" If you cannot do it alone, you start collaborating with others. That is the next step. That is how teamwork starts. You collaborate with biologists, engineers, or other specialists. You move to the second phase of your research- asking questions that are worth solving. Finally, you reach a stage where you start guiding others.

That is how we all become part of committees, suggest projects, etc. You do not just incorporate ideas; you continue what you are doing, but you help others understand and develop a critical mind. In the final stage, you think of a problem and find happiness. You see, problems need to be created.

Science moves in these stages. You may often ask questions for which answers may not be immediately available. Then, something happens somewhere else in another area. Every area grows and gets saturated, and then suddenly, something new emerges, and people take it up. You have to constantly look for ideas from other areas. Today's interdisciplinary science is popular because no single field can dominate entirely.

And as I said, it gives great pleasure to think of an idea, solve the problem, and find a solution. Sometimes, finding a solution is important. I think Rosalind Franklin said, "I can solve the problem, but what is important is why this is the only solution. Why are there no other solutions? Why is this the best solution?" That gives you more happiness. It is this quest for knowledge that drives us. You are not bound by anybody. Literature is available; open science and knowledge are accessible to all.

Even if I don't have any facilities, I can still think and write. That is what drives one in science. Many people give up because science is a hard path. But you must have that inner passion, that fire in the belly, to keep going.

For instance, I recently bought a book by Venkataraman called 'Why We Die'. It is a novel idea. Venkataraman went to India and worked in Cambridge. Now, he worries about why we die. Suppose there were no deaths; what would happen? Nobody funds research for that. It all comes to your mind. How much is dying a biological necessity, a philosophical necessity, or a social necessity? If everybody were alive, the population would keep growing. There is what is called homeostasis.

In science, you can keep asking questions. There is no limit to the questions you can ask. There is no such thing as a stupid question. That is what drives us. But to do science, people also have to make certain sacrifices. That is what drives me. Even today, I have a lab with four students working. It is rewarding to guide them. However, not everything will lead to a Nobel Prize.

Taking a question, solving a problem, and devising tools and techniques is one aspect of science. The second aspect is not just solving the problem but also publishing papers. Right? We have to write and share our findings. When you send a publication to a journal, someone you have never met or do not know reviews it. They assess your work and may say, "What a fantastic idea he has! He has done it!" and they accept the paper. Even today, for a scientist and everyone here, the greatest happiness comes when you get an email saying your publication has been accepted.

That is it. I might be working in isolation, doing something, but somebody in New York, Washington, Germany, Berlin, or somewhere else reads it and praises me. This shows that your thoughts are universal. Science is universal. That is the joy of doing science. That is what keeps me driven. I can keep doing it till the end of my life. You must not be afraid of criticism. There is no point in asking whether it is worth doing or not. Just do whatever your passion allows and ask the questions.

Today, it may not be relevant, but five years down the line, it may become relevant. That is what drives people.”

That is a perfect answer. I have also read that you completed one of your PhD degrees at Cambridge University. How much do you think foreign exposure is important to an Indian student? And if your answer is about the high-quality infrastructure, the better research group exposure, better pay, and all of it, why didn't you ever decide to settle over there with your own research group because of better pay and all of it?

“Good question. So, I did a second PhD. It was not intentional; I did not have any specific plan. I did it for a different reason. I completed a PhD at Delhi University, which takes about five years. As happens in every student's life, you get frustrated somewhere after the second or third year. Things don't work out. So, after the third year, I thought I should leave and go somewhere else. I was very fascinated with American universities at the time. They had a lot of literature. There was no email back then, so you had to write a letter to graduate schools. In response, they would send you big pamphlets, photographs, coursework details, and everything else.

I used to feel very happy looking at it, imagining, my God, why I should have been doing a PhD abroad and, you know, all the facilities are there. So, a professor from Cambridge came, and I interacted with him- he was doing an entirely different area. But the way he talked, for them, everything, that ab initio thinking.

What is important is to start from the electron structure and explain everything from there—ab initio thinking. Two important things in research are ab initio thinking and the ability to ask questions. I spent one day with him at Delhi University, and he impressed me so much that I thought I might go to Cambridge University.

So, I started applying for a scholarship. It was a government scholarship, and I got selected for it, but it took one and a half years.

By the time I completed my PhD at Delhi University. But after completing PhD, you can go for post-doctoral work where you don't take up this type of degree. So first, they asked me why I was going to Cambridge. Because of that fellowship, they advised me to avoid going to Oxford and Cambridge. I wouldn't get in as it was very highly competitive. But I showed them the letters my professor had written. Now, I want to work with one professor working on vitamin B12 and its synthesis. That is important for haemoglobin, chlorophyll, porphyrins, etc. I convinced them, and as a particular case, they allowed me to go to Cambridge. So, I went to Cambridge for this fellowship, which was given to me for ten months. It was a post-doctoral fellowship.

That was the rule at that time. So after going there, within one week, you know, the professor was not there. Another young lecturer was talking to me.

I was so impressed with that in just one week. I wanted to stay there for three years, not ten months. They suggested that since I already had a post-doctoral fellowship, I could stay for three years if I registered for a degree. The university was allowing people who already had a PhD to do so. So, I registered for a degree. 

When you register for a degree in Cambridge, you become a part of a college. The professor said it doesn't matter whether I get a degree; I already had a degree. By registering, I was getting a fellowship for three years. So that's the reason I registered. Luckily, I could finish within three years what it took five years here within three years. That's because of several reasons. One is, of course, the facilities there. But more than the facilities, it was the environment, so I took a lot of courses.

There were fantastic people. Each of them had written a book we were all following, a textbook by Peter Sykes. You know, Peter Sykes is known for Mechanisms of Organic Reactions. He was teaching a course, and many other professors cum authors were, too.

Everybody gave a course, their activity, or a book that everybody else uses. So, I attended all of the BSc lectures, sitting with BSc students every day in the morning. I could learn chemistry entirely in a new way. That's what made a difference. You know, ab initio thinking. A new method of teaching and to teach chemistry that is not memory. There is a logic in that kind of thing.

You see, science should start with a new idea. Many times in India, our choice of problem is that we don't work on new ideas.

We build on the existing ideas. That's what happens in most places. For whatever reason, it is our reasoning. That doesn't take us very far. I am making a general statement, but in many places, they work on general ideas- in many cases. UK was a fantastic experience because I was in a college system. In Cambridge, every other guy is a Nobel laureate. The humility, you know, people are so humble. Nobody feels proud that they’re a Nobel winner. You talk to them, and they’ll excellently explain things.

Humility and always thinking- these nerds; you can physically see it in them. That made a great impression on me. 

That's how I got a second PhD. And that was another experience. So, when you submit a thesis, even your MSc or dissertation, somebody has to read it, which usually takes two to three months to get evaluated and then receive a degree, after which there will be a defence. There, it was not like that. On a Sunday, I submitted my thesis. My supervisor came with me, submitted three copies to the university, and gave one copy back to me and said, "Okay, so-and-so is your examiner; you go meet him and give the copy to him.” So, I went to London and handed it over to so-and-so.

He said, “Can you give me one day to read your thesis?” on a Tuesday, he read it. On Wednesday, he came, took the exam, and I was done. On Thursday, I left. It's a straightforward system because their way of assessment is different. They look for an idea density. Even today, the idea density, or the propagation of new ideas, is very high in the Oxford-Cambridge area. In fact, the number of Nobel laureates who have come and the number of ideas they have implemented is equal to what they have done in Europe. That's what they say. But the thing is, they generate an idea but don't go on. Once the idea comes, Europeans and Americans will all start making it. But the original idea comes from there. So, they go for an idea.

 It is said that you give them (Oxford and Cambridge) a wall and ask them to jump over it, Americans will use high carpets, rope, etc., and try to cross the wall. Cambridge and Oxford burrow a hole and go underneath it to the other side.

It is like that. So, it is a great idea; they make you think. They build up when you talk to them about what is new and what is an idea. So, all these things had an effect.

 Whatever I have been able to do, it is only because of the training I got the way of thinking about approaching problems right from the basics. That made a difference to me. So, the second PhD was interesting. In Cambridge, you know, it has a different value than majorly from. But at Delhi University, I learnt something different. If I had this experience, I could have finished it after three years. But, what impressed me was the enquiry, understanding of the problem, and the pedagogy, i.e., how they teach concepts.

Even today, we see a lot of brain drain happening in the country. A lot of people go for PhDs, post-docs, and then they settle down there. So, how do you think about it?

"You see, one thing that is not in my mind is to settle down there because when I get this British Council fellowship, we have an agreement with the government. After all, the British Council funds it with the Indian government. There's an agreement that after our term ends, we return to India and serve in some institution for one year.

PhD training is very tough in the US compared to the UK, which focuses on idea density. In five years, you must write theses and learn everything: the value of numbers, kinetics, thermodynamics, and mechanisms. Doing a PhD in the US, you become such an expert- you can train very well as a form of training.

You know, for one thesis, you write all the hard copies of spectroscopy and get very good training. Additionally, you get exposed to a lot more problems.

The UK is a small place, whereas the US is much larger. The way they conduct science—so many visitors attending conferences, symposiums, and meeting people—creates a very exciting research ecosystem in the US. I've also been to Germany. Each country has its cultural aspects. However, in the US, they don't care who you are. For them, your ideas and merit count, and they overcome everything. Even today, I feel that despite any biases, the US is a country that allows the free flow of knowledge without discrimination.

But for various reasons, we eventually return. What's important is that going abroad—whether to the UK, Germany, or the US—and conducting research in different cultures in a competitive spirit provides crucial training and perspective. Some people in India may not have had this opportunity, but exceptions exist. Nonetheless, the supervisor relationship in India often influences us significantly. Abroad, it's different; individuals operate independently. There, you learn confidence; your ideas are not dismissed but encouraged, essential for personal and professional growth.

It is also important to learn science in a different culture. Competitiveness is important; hard work and culture greatly influence the research, apart from the infrastructure. The second most important thing is that in India, we interview somebody and say, “Oh, he is not good for a project.” The same guy goes abroad and does extremely well. The ambience and the environment there push the mediocre to average and the average to a higher level because of the environment. They bring the best out of people. Still, in India, our systems are not to bring the best out of people. So, abroad going and getting, you know, it is important. And you can come back and use that thing and start working here.

Even when PhD graduates from abroad return to India, the environment will not accept them. Then, you start compromising and become a part of the system. So, it is invariably evolution.

And the important thing is you go with an idea every day: I want to do this today. You can do it in the United States. When you leave, you have achieved all the goals.

India is not like that. You have a plan, but you would have ended the day doing everything else. We do not have that sense of privacy for others' time, etc. We do not value time. You go around gossiping, and there’s a lot of unplanned action."

I wanted to ask you a few questions about directorship. Not all scientists become good directors, but I have heard many superhuman stories about you. So, I used to live in the NCL quarters, and I have seen how NCL donated 100 acres of barren land to IISER Pune, and you transformed it into a mega campus. Today, it is the most preferred IISER for students, and IISER Tirupati is the fastest-growing IISER, one of the institutes you have founded. So, what were some of the secret things you implemented during your tenure as a director that transformed the research culture for an institute like IISER?

"When I joined NCL, I became head of their organic chemistry department.

I was there for almost 19 years. And it was good. I trained with Dr Mashelkar and Dr Shivaram, the other directors, and Paul Ratnaswamy, some other directors. Watching how they manage all the responsibility of making decisions and management was great. I mean, I learned something from them. I used to observe scientists. Although I did not appoint, in 19 years, I must have appointed two or three scientists. There were no positions. However, I was active in research, and my culture was very good at NCL. Then, for five years, I was in Hyderabad. As a chemist, I thought the future was focused on biology. So, when I returned from Cambridge after my PhD, I immediately went to CCMB Hyderabad.

We had a director who was building a new laboratory in CCMB. So, right from the beginning, I was watching – how do you create something without the physical structure? However, I never knew then that someday I would have to build buildings and everything. He was recruiting scientists, and I watched how he did it—what kind of attributes he looked for in new faculty. This learning process happened subconsciously in the background. Often, we believe we're acting independently, but many environmental factors influence our subconscious mind.

But then I wanted to focus on chemistry, particularly DNA synthesis. Working in a biology lab was becoming difficult. We had a fantastic time with one of the biochemistry heads at NCL, who used to come to NCL and CCMB as a council member. Although he was a biologist, he would get excited about chemistry. He once said, "Doing biology in a chemistry lab is easy, but doing chemistry in a biology lab is always difficult."

Because of him, I shifted in 1987. At that time, everyone was working on insecticides and pesticides. DNA and peptides were a new language for them at NCL. I was somewhat of an outcast since they were all focused on industrial development and chemical processes. They were taking patents and transferring technology, but none of that applied to my work with DNA.

But they wanted to start a new area and let me get it. It gave me a lot of freedom, you know. And I could never do that kind of chemistry, process development, etc. I will do chemistry, which is required of me. So, I learned a lot of things by observing people, managing big institutions with a diversity of people, and doing so diplomatically to get the best out of people. This environment shaped me, even though I never aspired to it. But I was fond of teaching and frequently taught at Pune University.

So, somewhere around 2005, when Dr. Sourav became the director, PhD coursework was introduced at NCL. He asked me to set up the academic PhD coursework because I was already teaching. Sourav Pal and I started the coursework and brought an academic culture to NCL.

Seeing this, when they decided that the first IISER would be in Pune, Shivaram asked me if I was interested, having observed my attributes. I said, "Okay, let me try it out." I didn't know how things would unfold, so I approached it with an open mind, like an unformatted disk. On the first day, there was a big piece of land. In fact, we used to go and bury all other chemicals there on that land.

On the first day, they gave me a small briefcase of money, and told me to go ahead and get started. There was an idea of how research should be developed, etc. From that day, I realized I needed to undergo a phase shift in my thinking. I had been appointed as a director, and I had to establish myself. I was very clear about the importance of academics: faculty are the key. The first priority is the creation of facilities; the second is the recruitment of faculty because they are responsible for both research and teaching. So, I spent a lot of time advertising, recruiting people, and talking to them. The main factor for success was attracting good faculty.

At that time, attracting good faculty was not very easy because they would prefer to join IIT, IISc, etc. However, we could attract people with money and a good startup grant, allowing them to come and set up their labs. Additionally, the ability to convert challenges into opportunities was crucial. For instance, we started with NCL Innovation Park.

I don't know what gave me the energy, but I was always thinking and still doing research with my group. This often meant burning the midnight oil. During this time, quick decision-making was essential. Nothing should be left unresolved, whether big or small. You make decisions one way or the other because not making decisions can cause even more problems.

Another important factor was the ability to read people's minds—a sort of sixth sense.

Use the right person for the right job; that is crucial. Placing someone in the wrong role can be detrimental. And avoid bias. If someone recommends a candidate, I will only hire them if I am convinced of their suitability. And learning about government is also very, very important. After all, I am spending government money, and while you cannot change the rules, you can achieve your goals if you know the rules well.

The greatest lesson I learned in IISER is that you cannot change the government rules, but if you understand them thoroughly, you can get what you want. When we went to the Pashan sector and hired a building, it was the first case of a government institution hiring a private building. This experience taught me a lot about bureaucracy and how to convince others. We paid a significant amount of rent, established a lab, and dealt with CPWD matters. One thing I learned from CCMB is that the director's job is to bring in funding, set up facilities, and handle everything necessary to support the recruitment of good faculty.

When a new faculty joins, he should be able to do the first experiment the next day. Can you provide that kind of facility? So, first, build it and hire faculty. They should not spend time running around, doing this, that, etc. You should be there and do good work after 2-3 years. Then, you will automatically attract funds. So, that was the second principle. So, there we established a fantastic, very modern laboratory. Because I got to know all the rules, plan it and seek advice.

By talking to people, you observe all the ideas. I was very open-minded, you know, to take it. And having good colleagues around you is very, very important. So, we did that and then slowly shifted. It just happened. I didn't make any effort; a solution already arises when considering a problem. I said Pune was a story of, you know, not just me. 

Then, I had a very good colleague, Shashidhara. I don't know whether you have heard the name. He is the director of NCBS now. And he was in CCMB earlier. I did not know him. He was my junior to me. However, when I met him, I had a strong sixth sense (like I was talking about) that I should bring him on board. I managed to get him involved. In the first four years, we struggled to attract professors in physics and mathematics. Pune attracted faculty, perhaps because of the location or my method of selection, which involved bringing people together.  

So, we got that. For the first four or five years, Shashidhara became the head of mathematics and biology, while I was the head of chemistry and physics. That helped me learn quite a lot. The second thing, which is the greatest thing I learned in Pune, is that every discipline has its own culture. Chemistry has a culture, physics has a culture, as do mathematics, biology, engineering, and the social sciences.

Every discipline has its own culture. Chemistry is the simplest of them. You just give them a balance and a vacuum pump, and they will go on publishing papers. Whether you have one biologist or ten biologists, biology requires the same infrastructure, autoclave, centrifuge, and microscope, and it doesn't matter. There are two types of physics: theoretical physics and experimental physics.  Experimentalists have to build something- an instrument for a problem. It's very tough. And it’s also expensive to provide them with everything. Mathematicians are a rare species on Earth. They're in a different world, you know. I mean, they don't ask you anything, they don't talk to you – they're in their own world. But they feel bad that they're not recognised and don't get what they want. 

One day, I thought, why are they always sad sacks when I talk to them? So, when I went and talked to a mathematician, he said, “All we want is a big blackboard. We want to write things.” They don't like PowerPoint screens and all that. Okay, that's so easy – provide a big blackboard and a chalk. The next thing they said was, “We want a coffee machine. We drink a lot of coffee. We convert coffee into theorems.” Okay, that’s nothing, you know. One will be a spectrophotometer.

“We want a lot of visitors.” Okay, invite any number of visitors. Visitors will come, but they don't even talk to each other.

So that’s what it’s like, but that is necessary for good mathematicians. So, understanding the culture, supporting them – that's what Pune became because I didn't fix a rule. And mathematicians, physicists, chemists – I learned about all the cultures and supported them how they must be supported.

I learned quite a lot about building construction. I'm not an engineer- I know how to tender, deal with the architect, and deal with contractors.

You must have seen IIT Tirupati, of course.

One is the academic component, having committees and deans look at all the academics I was new to. In CSIR labs, it was not there. So, the second thing I learned was all about construction. I used to take a lot of interest in designing labs or driving. One thing that happened at NCL was that in 19 years, I used to practice going to international conferences or visiting institutions every year. I used to visit so many countries, but in India, this is very difficult. The faculty don't receive sufficient money to visit a conference abroad; the government is very stingy. But somehow, I managed to, which gave me much experience seeing other institutes.

Involving faculty was the key. So, finally, it happened, and IISER Pune flagged off.

Luckily, the faculty did very well in terms of research and teaching. I still remember our first and second batch of students who graduated. I remember all of them.

They're doing very well everywhere. So, at that point, the important thing was not just IISER Pune. There were five other IISERs, with a one-year difference. Pune and Calcutta came.

We had to build a brand value for them. IITs are very well known, and so is IISc. Our main flagship program is our divergent B.S-M.S. program, which none of the other institutions had. It has to be the first two years of the breadth of research. You study physics, chemistry, maths, biology, everything. Because when you come from class 12, you study either biology or mathematics. So, bring them all to the same platform, and then, by the end of two years, they will know their interest.  When they come, they might want to become an astrophysicist. Afterwards, they may become a biologist or vice versa. So, once you find interest, after the third and fourth year, you study subjects.

Take courses deep into that. So, in the fifth year, you do an entire project. Even today, IISERs give a very good balance.

The breadth of research, depth of research, breadth of science, and the research. And that was what was appreciated by a lot of international universities. People would say, “My God, why didn't we think of this kind of thing?”

Prof C.N.R. Rao gave the idea. But he went away once he put that idea into practice; we all had to execute it. Then, we visited a lot of institutions and talked to them about IISERs. So, the first five years were spent building a brand name. After the fourth year, the students graduated, and some went for internships. About 20% even went abroad for fellowships.

I had a very good colleague in Shashi. We took everything meticulously, whether it was a classroom, laboratory, or house. Perfectionism, as much as possible.

As a director, you should manage your time in a relaxed way. Socially, bring people together in a social context. Of course, Pune is also a city, you know, where people would come, because the city is so good. Tirupati was a different challenge. Because there is nothing apart from the Balaji temple. There is nothing else there, you know. I mean, you have been there. But the best thing was the first day I met Professor Satyanarayana, and we hit it off right from day one. In fact, the first day of our land and even the inauguration was on the land, which is what you call foundation day.

It happened on IISER’s land- all 3, IIT, IISER and IIIT Tirupati. So, from the first day we started, we had to look for a temporary campus there. Satyanarayana knew a lot more, even the locals, being Telugu, whereas I had a disadvantage. But, he, you know, is very good.

We knew that we had a big responsibility. And luckily, the government supported us.

He was a civil engineer. His knowledge of construction is much more than mine. But, since I had done IISER Pune, I, too, knew something about it. So, whenever I had doubts, I would consult him. So, the two buildings also are entirely campuses of a different architectural style. Different entirely, you know.

Again, what happened in Tirupati was that attracting good faculty to Tirupati is not always easy- lack of facilities- schools and hospitals. Though people joined because they knew IIT and IISER, we always used to feel guilty about not being able to provide facilities.  Luckily, Amara Raja Hospital came up in Renigunta. That happened, and that problem was solved. Well, education is now available. The KV school has started at IIT.

Now, the campus is complete, and things are moving. So, problems are different. The worst was the two-year COVID. It did a lot of irreparable damage. You know, see, faculty are joining. They want to start their research. I take PhD students, and COVID hit. Everybody had to go away. Nothing could be done. So, the faculty all trailed behind by about two to three years in the research. They could not establish a group. In Pune, there were no such problems. And, of course, I had a lot of experience in IISER Pune. One was that building trust is very important in the faculty and the non-teaching faculty, and I have clearly mentioned that the administration should never become powerful.

They should assist the faculty. For me, faculty is a key element in any institution. They do research. They publish papers; they do teaching. The rest of it is the output of those things, right? So, that is the emphasis I gave. Create a good environment for them to work. They should not feel the pressure of bureaucracy. So, I was very clear with the bureaucratic people. You find rules, you know. I mean, they will not know the rules. They will make mistakes. But you should tell them how to do the same thing. But you should give them what they want. So, trust is built. And I was highly accessible. Only now, because I had an online meeting, did I close the door; otherwise, the door would always be open because I have been appointed to address the faculty problems and students' problems. In fact, I had said you do not have to make an appointment. Accessibility is important. If I do not know their problems, then how will I solve them? I cannot be living in my own world.

You have to develop your own style of function. I am not saying that what I did was the most appropriate thing. That was my way of working. Probably, I succeeded. But, everybody cannot follow that. Your personality should match your style of function- my personality is very free; I trust people. If they say something, I do it. I trust them. I have always trusted people, which has helped me - people responded to that trust—getting extraordinary things done by ordinary people. That is what management leadership is.

We always say like abroad. Everything is done on their own. They have to only go about making money.  In India, you are responsible for everything, including the students."

When you were the director, could you carry out independent research, too? Were you able to devote enough time to your students? 

"Yes. I have been publishing papers. I mean, it was less- I used to keep the weekends only for students because weekdays were always difficult.  There is not much administration- we will have group meetings. At NCL, I used to keep visiting my lab and devote enough time to the students. However, when I became the director, I could not visit their lab as often.

But I kept working, and I kept up with research; otherwise, you feel even more frustrated when something does not work. The research was like a stressbuster."

You have worked in so many different areas - One is Peptide nucleic acids. Then, you moved into collagen mimetics, which has applications in tissue engineering. And finally, DNA nanotechnology which is used for drug delivery. How did you transition into all of these areas so easily? If you have a research group, it also requires aligning the students with your new areas, right?

"Managing a research group working in different areas is a challenge. I had worked on organic chemistry during my PhD days. But when I joined CCMB Hyderabad, I became interested in DNA. There were no machines, and there was no way of making DNA. It was not accessible - but it was required. Short sequences, primers, and enzymes were required for genetic engineering. So, I was the only chemist when I joined CCMB Hyderabad, a cellular microbiology lab. I was doing something else in physical chemistry earlier but didn’t see it go much further.

I realised that I am an organic chemist- so why don't I learn and make DNA for them? That was my idea. So, I returned to Cambridge for the 2nd time with my director’s support.  This time, I went to the molecular biology laboratory, where many Nobel Prize winners- like Watson- worked. There was a Mike Gate who had worked with Khorana, but he was new.

So, I went there for three months I spent learning how to make DNA fragments. I was given the problem of making 20 milligrams, which was difficult.

People were making nanograms. Nanogram to milligram is a big scale-up. Today, people are making tons. At that time, the machine was not there. After three months, I returned to set up a lab for DNA synthesis- not natural DNA but modified DNA for probes and other purposes. However, I realised I wouldn’t get enough chemistry students at CCMB in my group, as their PhD program was focused on biology. I got a student in organic chemistry, and he did something. Meanwhile, I built a synthesizer and learnt about machine building for chemistry. After that, I came to NCL. In NCL, everything was available. The reagents were available, as were the chemistry students. So, I proceeded with my research on DNA. So, I started making modified DNA. Just to remind you, in India, we have the mindset that if any new area comes in, we must enter that area. Then, you become the literature. But after 5-6 years. You start working in by the time. Somebody else has contributed more, and generating new things is difficult.

DNA was tough. Making RNA also. Making PNA was much easier. So, immediately, I got to the PNA area. Let us make some modifications. PNA is usually a linear molecule. I wanted to make it look like DNA. I had to make a five membered ring.  I could make a proline ring and make PNA out of that.

For that. I wanted 4 amino proline- proline is unsubstituted but a substitution in the 4th position and amino. For the synthesis of PNA, I did literature and found that it can be made from 4 hydroxy proline to 4 amino proline, and 4 hydroxy proline is a component of the collagen. Proline, hydroxyproline, and glycine are 3 peptides repeat in collagen.

That was one. The second thing was when I was at CCMB; there was a very well-known Prof. G.N. Ramachandran. Now, G.N. Ramachandran is one person from India who has become a textbook material. In any biochemistry textbook, you take, there is something called the Ramachandran plot if you have studied protein physics. When I came to CCMB, he was the chairman of my selection committee. I was very inspired by him- a straightforward person.

He is the one who gave the structure to collagen in 1954.

In 1950, Linus Pauling gave the alpha-helical structure- one of the greatest of the 20th century. That is the single helix. The double helix was solved by Watson and Crick and Rosalind Franklin. But for some reason, collagen nobody gets interested in.

DNA is very important, but collagen? Even dead bodies have collagen. But nobody is interested. Everyone then shifted to try to solve its structure, unsuccessfully. But G. N. Ramachandran, who worked at Madras University, published a paper in Nature. The first paper is a triple helix and not a double helix. Yes, triple helix collagen structure.

One distance he measured, around 0.2 angstroms, was less than the actual structure. They put one water molecule. It is like a hydrogen bonding or something. Watson and Crick, and Linus Pauling- particularly Watson and Crick- could not process that this man could do all this, and they later refuted his research by directly claiming that his measurements were totally wrong despite him giving the entire concept, which was cruel.

This is how I delved deeper into collagen.

So, what happens in the acidic state will be amine with net charge +1 will be cationic, and when it’s neutral, it’ll be 50-50. Alkaline pH- only NH2 is present. So, then, we need a lot of matrices. We published a few papers, and a few pages emerged as diversions. We recently wrote a paper about combining collagen triple helix with a PNA. So, that is the work which we have just, you know, sent the paper. So, it has a triple helix, a PNA strand, and PNA can bind to DNA. So, if I take one collagen triplex with three PNA strands and make put DNA, you know it binds and forms a duplex. DNA is then designed in such a way that another collagen can come. So, you can cross-link them through PNA DNA, right? That is the last of my collagen work we have done.

That’s how that started. DNA nanotechnology started because, in the 2000s, nanotechnology came. We had one scientist in NCL, and we used to sit and talk, you know, simply, and he could make nanoparticles at that time. Making itself was a big thing used to make gold nanoparticles, etc. He told me what I should do if I had this nanoparticle, what I should do, etc.

So, you know, just by sitting at the coffee table, we said, can we add nanoparticles to DNA? Can we hook it up like that? We used to think, and we started working. We published about 12 papers on DNA nanoparticle interaction. One of the earliest these things is how I come into nanoparticles. and of course, he left, and then I continued; then we made DNA nanoparticles to check their interactions because these things bind to the base. So, that is how DNA nanotechnology came. Today, we make sequences and then add silver and gold to create many more structures. That is the birth of DNA nanotechnology entirely. So, whenever it comes, you put one new student in and ask them to start working on that; that is how it happened. But it is good. I enjoyed, you know, these new ideas that came up."

I have a personal question about DNA Nanotechnology. DNA nanotechnology is extensively used in drug delivery, right? I read one of the papers of Prof. T. Govindaraju where he was talking about Tannic acid, which is a potential drug for Alzheimer's disease because it has a two-in-one advantage - it can destroy the amyloid beta plaques. It can also reduce the reductive oxidation species concentration to avoid ferroptosis, solving the issue upto a good margin because Alzheimer’s is multifactorial in nature. Still, the problem is that it is a polyphenol, which degrades very easily. Once you find a drug, crossing the blood-brain barrier becomes a tough challenge. So, what they are trying to do right now is make derivatives of tannic acid so that they can use it for drug delivery by solving the problem of polyphenol degradation. But I asked him why we do not encapsulate it inside a gold nanoparticle or something similar. It has effectively proven to cross the BBB, thereby acting as an efficient drug delivery vehicle. What do you think is the advantage that DNA nanotechnology for drug delivery offers over encapsulating it using gold nanoparticles or, say, the new revolution of quantum dots?

"See, there are two ways. One is the DNA. If you design sequences, they can assume different shapes, and then they can, you know, encompass a drug as you know, for example, zeolites, cyclodextrin. There are a lot of drug delivery systems that bind them in a non-covenant way to make it, you know, that is there, but the real problem is the DNA itself does not go inside the cells very well. People are trying to find out how you can deliver the drug itself. You can trap the drug inside DNA. How do you deliver it inside because DNA has a lot of negative charges? Membranes have negative charges- it does not go inside."

So, why does it have so much potential for drug delivery?

"What they do is that you deliver by attaching it to something and taking it inside, not per se as such. So, you have to attach it to a cationic moiety like some lipid, attach it to some membrane-recognizing ligand, and then put it inside.

Of course, once you go inside, the rate is easy because there are several in which you have DNA. It is expensive stuff- DNA is expensive and feasible academically, but practically, it is a very expensive way of using DNA because it itself is a drug. For example, the mRNA vaccine we got during COVID uses mRNA as a drug that goes there and then synthesizes the proteins for which antibodies are developed.

So, academically, it is good, but it is very difficult to become practical because of the costs. Instead, you should try using cheap material for delivery, like soap, detergents, lipid particles, etc., or you can use silicon nanoparticles or some other cationic species. For the making process, you take a plasmid DNA and add a lot more short DNAs, then they give the shape, and finally, you trap a drug in that."

That’s a convincing answer. The next question concerns one of the arguments I have heard about research: that research nowadays is mainly restricted to numbers- citations, H index, and all of them. So, do you think there is a difference in research compared to 30 years ago and today? Do you think researchers are not taking risks because they think it might compromise the numbers or something similar?

"Risk-taking is a part of the research, but what these things have done is, a long time back, literature was less. There were not so many papers coming, and the number of journals was less.

So, if you are working in an area where you know who is good, who is doing what is, etc, then you can evaluate research per se based on the science part, not too much in the journals. Nature is always good, and Science is prestigious too, but the best in organic chemistry work went to Tetrahedron, Tetrahedron letters. So, many of them, you had a community feeling. All the physical chemists will publish in their community journal. So, as the area started improving and interdisciplinarity came, people came up with new ideas to evaluate research- the number of citations, the H Index to assess the researcher, and the impact factor to assess the journal's quality.

So, the higher the impact factor, the better the journal; that became a golden rule, but some people went against the impact factor. For instance, the impact factor depends upon the area. If you are working in theoretical physics, not many journals are there, like mathematics, which affects citations, publications and the impact factor. So, the citation depends upon the number of people working in that area. Right when an area starts, it’ll have very few people. After that, more people work, and citations will increase; thus, citation is not a basic property. It is what you call a colligative property. It depends upon so many factors. 

When you publish a paper, you should not look solely at the higher impact factors, like nature, which has a very large number. Some kinds of papers from different fields can be geology papers, biology papers, high energy physics, etc. Now, you publish a paper in Nature, and you can brag about it. But how did nature get that impact factor? That impact factor does not mean that every article published had so many citations. Suppose there is one breakthrough paper that 10,000 people may have cited, but your paper may not have been cited by 10 people. You are a beneficiary of that paper because the number of citations will increase. So, the impact factor does not judge the quality of your science; it only tells about the quality of the journal you have published. You may publish an article in a journal of high impact factor, but after 10 years, you may or may not have citations.

What is the better indication is how many people cite your paper, which can happen even with journals of low impact factor. For example, if you publish an organic chemistry paper in Nature, organic chemists do not read that, no matter how good your paper may be. So you will not get many citations. Instead, I am the chief editor of the journal ACS Omega. I started the whole journal, so I had to worry if my impact factor was less, which meant my journal was not that good.

The impact factor should concern the general editors and not the authors. Instead, there is a time-dependent phenomenon of citations.

So, today, if you published a paper 15-20 years back and people are still citing it, your work is outstanding, even though it has not been published in a well-known journal. So, now only people are realizing the pitfalls faculty were hired because of impact factors, etc. Then, we saw the emergence of new metrics like H-Index.

So, to some extent, all these metrics are indicating, but one should not make a complete judgment based on those metrics. Somehow, China has been corrupted. You are given a thousand dollars if you publish in a general high-impact factor. Monetary benefits are given, but that does not reflect your science just because you published it.

I also give a lot of lectures on how to write manuscripts and how to choose a journal. We mentioned these things: when you want to choose a journal, do not choose a journal because of the impact factor. You select a journal where your community, where you are working, reads the journal. There is a journal called Biochemistry in ACS. Its impact factor is only 3.5, but it is tough to publish, whereas a higher-impact journal may also be easier to publish. Now, many more metrics, as you know, are called altmetrics. People say, " My paper has been tweeted so many times” on social media. All this has no meaning for the development of science. Now, even citation downloading or citations are politics. I may publish a paper by a well-known scientist, but he may not cite my paper at all intentionally because he wants to get the credit, so citation politics is happening. So, even that is not a true indicator. Now, there is a new trend happening in China and Japan. They have been told to cite only those papers belonging to their country because that country's numbers go up. So, all that you know is that it is a question of numbers and metrics. It does not reflect the quality of science. 

If you cannot evaluate the quality of science, then we have to go by numbers. People who are experts know you might have published in a lower journal, but they still recognize you. People who are not experts, the selection committee, and people who shortlist will only go by numbers, which is wrong.

So, you have to publish in a journal where your community people working in your area read them, you bring them to their attention, they will quote you, they will respect you, they will value, and that helps push the science that is what is essential. Somebody publishing in Nature himself may need to be reading Nature or Science. So, these are the distorted things now; even more difficult things are coming up in the journal publication. They are called open-access journals to promote transparency in the world. So, they started it called open access journals, but journals are against it because readers wouldn’t subscribe to them anymore. These journals promise more views and readers but require the author to give money from their own pockets or funds, which may be expensive for a scientist from India. Some European countries have mentioned that 10% of the grant is for such publishing. Information that knowledge generated out of that research should be freely available to the public was the idea.

If I make an open-access journal, then the author has to pay. If I had to pay, I would have to get a research grant from the government. So, the government says okay, I have given you a grant to make it freely accessible. By making it open access, what is the advantage from the author's point of view compared to a subscription model? Only those who can read who pay money will have access to that. Others will not even come to know about your work in a subscription model. But with open access, anybody can download it when it appears in the press. So, your accessibility to others increases- your citation should go up. So, somewhere, either you pay, or others have to pay.

They said all journals would be open-access in about another five years. Now, journals are resisting- they want money from the authors. If it is too much, then you will say if I publish here, I have to pay five hundred dollars. If I publish, I can pay a hundred dollars; I will publish, but that may not be the right journal. So, another kind of bias will come. So, impact factor, coming back to that- one should not judge entirely by that. You should judge by whether it is published in a journal, which is important for that area, and citations, of course, tell you about the quality."

That was very informative. Last but not the least, I had a question about proximity. Institutes in proximity foster a collaborative nature and help improve the research thereby improving the growth of the institutes. For instance, how the NCL-IISER Pune proximity helped IISER Pune grow so much is an example. Even in the US, sister institutes MIT and Harvard are world-famous examples, where they collaborated multiple times- one example is the creation of the Broad Institute for Biomedical Engineering. Similarly, regarding IISER Tirupati and IIT Tirupati, what is the future and potential of these institutes in terms of collaboration?

"When IISER was established in Pune, we had a tremendous locational advantage- NCL was next door, ARDE-DRDO was beside it, IITM was opposite, and Pune University and NCCS were nearby. No other institute had this luxury. Pune was the Oxford of the east, and proximity will undoubtedly help, particularly for teaching and academics. You can invite visiting faculty to teach a course in case of faculty shortage, etc. However, in the case of research, it has yet to go as far as expected. How many joint publications have come from NCL and IISER Pune? Very, very few. The distance between them, but very few publications through collaborative research, speaks a lot. On the other hand, people might have published in collaboration with Oxford or Cambridge even without being nearer. So proximity is good but only helpful in boosting research if people recognize it and use each other's facilities. That happens only when their interest is complementary. For example, one thing in IISER Pune was that I did not recruit too many faculty in synthetic organic chemistry because NCL has a very strong department, so we could always take them to come and teach. But that, too, did not happen very much- not many people from NCL came to IISER. Prof. Sourav Pal was teaching theoretical chemistry when we did not have faculty, so ultimately, interaction depends on proximity and individual connections.

For IISER Pune, we only recruited faculty where needed and used institutions' proximity to our advantage in teaching. In fact, in IISER Pune and Tirupati, we did not recruit anybody in data science or computer science because engineering institutions have faculty for that. On the other hand, they have chemistry but didn't have undergraduate labs for which they used ours. In those new institutions, we can take advantage of the proximity to academics and facilities. Still, if people don't take advantage of that, then there is no use, and that happens only when you have a one-to-one interaction, and that intent should be complementary. This is the case even in IISER-IIT Tirupati, and it depends on how well the one-on-one interactions develop between the faculty in the coming years for faculty, labs and complimentary facilities."

That makes sense. With this, I came to the end of the questions, and I’m so grateful to you for giving me 2 hours of your time for this questionnaire with so many insightful answers. I hope to see you again sometime around campus soon, sir!