The Silverfish

This interview developed from initial conversations that took place in 2025, when Mani Ramaswami visited the Archives at NCBS exhibition, ‘Untitled, Undated’, and shared his thoughts on an exhibit displaying the cone snail/conotoxin project by biologist K S Krishnan. A few weeks later, the exhibition curator, Dhatri, sat down with Mani, who joined online from his office in Trinity College, Dublin to interview him on all things K S Krishnan, snails, travels, and archives. Mani Ramaswami is a Professor of Neurogenetics in Trinity College Dublin and Adjunct Professor in the National Centre for Biological Sciences (NCBS), Bangalore. He was a good friend of K S Krishnan and one of the collaborators involved with the cone snail project. 

What was your first introduction to K S Krishnan?

There were multiple introductions. I was a student of chemistry in IIT Delhi. One of my friends, and a fellow chemistry student, Kalpana Krishnaswami, had worked in TIFR Bombay in 1982 on a summer project and her advisor was K S Krishnan. My summer project in 1983 was with P Balaram in IISc and I also heard many stories of Krishnan’s time in Balaram’s lab. So, I felt I knew him before we actually met. When I went on to do my PhD in Caltech, I met many people from TIFR, including K VijayRaghavan, Obaid Siddiqi, Gotam Jarori, and Tadmiri Venkatesh. So, in 1986, when I went to visit my parents, I travelled through TIFR Bombay where I first met K S Krishnan in person. He was a birdwatcher, even though it was an odd thing to do in those days. I was also a birdwatcher when I was in school and so I think we formed a pretty instant friendship.

Did his interest in birds and natural history feed into work within the lab?

I think the cone snail project was the first time that it began to feed into things he was doing in the lab. Both Krishnan and I had an interest in natural history. And if we did what we wanted to do, we’d probably have worked on natural history in one form or the other. But we didn’t. He did engineering. I went to IIT and so on. So the conotoxin project was this, really the launch, I think, of starting to work on natural history things.

What led to the conotoxin project?

To Krishnan, I think that the idea of neurotoxins was always interesting because a lot of studies of synaptic transmission were also with neurotoxins. And some of the peptides that are used by bees to affect membranes, melittin and so on, that Balaram’s lab had worked on, are also toxins. I was a professor in the University of Arizona and Krishnan came to visit me several times there. But I also bumped into Baldomero (“Toto”) Olivera on more than one occasion. He had pioneered work on conotoxins starting from his time in the Philippines and said “You know, there are all these very interesting cone snails in India that I’ve never looked at, and they would be interesting to study.” So that was probably the start of it. And I talked to Krishnan about it. He said, “It sounds very interesting.”

I think it was January of 2001. I was visiting my aunt in Ernakulam. She had been a marine biologist before she became a mother and she said, “Oh, one of my seniors is the director of this place called Central Marine Fisheries Research Institute (CMFRI) in Ernakulam, you can drop by and talk to him.” So I dropped in and asked this person, whose name was Mohan Joseph Modayil, “Do you know somebody working on cone snails in India?” And he said, “Oh, there’s somebody from CMFRI in Bombay named Venkateswaran, who may know. Then I told Krishnan about Venkateswaran, who later invited Venkateswaran to do a talk in TIFR Bombay. And they hit it off and that’s kind of how it began. Venkateswaran was a very interesting person. He said, “My name is Venkateswaran, but you can call me Venkatoxin.”

I found this map in Krishnan’s papers, which hints at some of the travel involved along the coastlines of India for the project. What was working outside of a biology lab like?

It was sort of an adventure. We didn’t know how to find cone snails. Cone snails live at multiple levels – some of them are in shallow water, some of the more exciting ones are extremely deep waters. We went with Venkateswaran to work with his supervisor, Fernando, who was in Porto Novo, Tamil Nadu. It became clear quite quickly that Venkateswaran talked a very good game but didn’t seem to have ever found a cone snail. So here we were with this guide, who didn’t know where we were going. My mother decided to come along because she likes to travel and so did my cousin who is a professor at Berkeley in Electrical Engineering because he wanted a free trip. The four of us went, including Krishnan, and met Fernando. He was fairly mysterious. I don’t think he ever collected cone snails, although he was broadly interested and very knowledgeable in marine biology. We went to a few places and pretty much found nothing except for a few shells and many dead fish in the middle of the beach. One day, we went to a shell dealer named Raja Mohammed. We saw how he was making various interesting things from the shells and he said he gets them from fishermen who go trawling for shrimp off of some beach. And if we go to that beach at the time when [the fishermen] are coming in, maybe we can look at what their by-catch is.

So, we went there at the end of June, it was very very hot. The main trawlers would park some distance away and they would transfer their catch on to these things called catamarans, which were hollowed out wood logs and they would bring their stuff out back over the water in the shimmering heat.

They came in and spread their by-catch around and there were all these things in them, it was pretty wild. And among all the creatures, there were cone snails as well. After we got the cone snails, we had to figure out what to do. A bunch of very energetic students who were masters students in Porto Novo, came along and participated in helping dissecting the venom duct and putting them in alcohol. So for many days, I thought this is never going to work, we are never going to find anything, and all of a sudden there was an explosion of cone snails.

The map also details some timings, are those indicative of the shop timings or catches?

From the little bit I know about fishing, I know that the catches come in based on the tides. I think the mornings just happened to be Krishnan’s timetable, he was an early bird. Raja Mohammed never went to the beach, he was just the shell guy. He would tell the people what kind of shells he wanted and the shells would be delivered to him. He had a way of cleaning and processing the shells, they stank to high heavens after getting the creature out of them. He would then bury them in sand, and polish them and make lamps and curtains and all sorts of things with them. A throw-away is, when they had conches, that were always sealed by this little operculum, which was taken out by these fishermen and put in a box. And these were sent off to China where they were considered to be aphrodisiacs or something. But Fernando pointed out to me that they always hold it in the left hand when they do it and that the left-handed conch shells are the ones which are most common and those would fit nicely in your hand like this. But the right-handed conch shells would be curved differently and those were the ones which were worth a lot of money because for religious purposes people always wanted them. So the sacred conch shells are always right-handed ones. There were these sub-different worlds of shell dealers and shells that were also opened up during the trip.

Did you face any challenges during these travels?

There were always, you know, some adventures, but nothing that was unpleasant. Like once, almost certainly in 2002, on the way to Rameshwaram, there was some guy, I forget who it was, some smuggler or some supposed terrorist, who the army was looking for. And so, we kept getting stopped on the road. Krishnan wasn’t there. [Editor’s note: the incident referred to is the 1998 Coimbatore bombings]. 

Toto and Toto’s wife, Lulu, and my mother and I were going in this car from Madurai to Rameshwaram. And we kept getting stopped by these guys with guns and things on the way. So, to me and my mother, they just looked like young boys with guns who were hoping not to find any terrorist. But Lulu was getting a bit scared by the whole thing. At the time, we were also staying in this little hotel in Rameshwaram. At three in the morning, all of a sudden, there was a huge racket. There were lights coming on and people all saying, “time to go, time to go! shooting, shooting, shooting!” And she got incredibly scared. But it turns out that it was a movie company that was around and had to go to the beach to shoot before the sun came up.

Do you remember which movie this was?

I can’t remember, but if we find the exact dates, I might be able to find out.

You mentioned your mother accompanying you and the other scientists. What was this trip like for her?

For my mother, it was completely the first time, but she was… Krishnan and I were both philosophical about [the cone snails]. My mother was not going to quit. She came all the way to find the damn things. She was with us all the way through. I have some photographs of her, the first time we saw them, pointing at them.

What about Toto? Was he onboarded as a collaborator to the project immediately or later in 2008, as a letter from the Archives indicates?

So, Toto actually came to India, I think, in 2002. We invited him over. That was our second trip looking at Conus species. I wrote to Toto because he was one of the people who set us up, told us that this was an open area, because you need to know enough about the field to know what’s an open space. And so we went further south to Rameshwaram with him. Toto had come here well before this letter from 2008 was written. Lots of these letters are sort of formalities when you’re trying to write for a grant, you show that you have somebody on board. And Toto was also, you know, he was passionate about [his work]. And so if you’re around people who love doing their work, you don’t think about collaborating, you’re just working together.

Now that you mention formalities, what were the administrative aspects of doing this kind of field work?

For actually going and finding the cone snails and collecting them, I can’t remember ever asking for any permission from anybody. But on the other hand, we didn’t do this ourselves. The actual collections were done with Fernando initially, almost completely. And he was in Porto Novo in a marine biology institute there. So we didn’t actually do the collections. We were part of the trip, but he really led it. The grant application was to get money for a sequencing project from the Department of Biotechnology (DBT). For that, permissions are not required as it’s just molecular biology. Once you get the prep, you do it. But you have to be a professor or have a permanent academic position in India to submit such projects. And so Krishnan and Balaram took that responsibility. And, not to give myself too much credit, I wrote the first draft of that proposal to DBT.

Between you and Krishnan, what did the work and responsibilities look like? 

I think none of this would have happened without Krishnan. He was a man who everybody in India trusted because he was a completely pure-hearted person who was really interested in stuff. He wasn’t interested in credit. He was interested in getting something done and having fun. And that purity, you know, was inspiring for everybody and was totally clear when you’re dealing with him. So, Krishnan was really critical. I don’t want to take anything away from Krishnan at all. But in terms of the formalities, I don’t think he had so much patience with the formalities of proposal writing and getting letters of collaboration from people and that kind of thing. So, you know, I did a lot of the… I fronted up with people that Krishnan was not very good at fronting up with and with functions he wasn’t very good at doing. But he did a lot of things which I would not be so good at.

In his collection, I found a portrait he had made of you…

A very lousy portrait…(laughs)

I was just about to ask you to comment on his artistic abilities! But did he draw often?

Absolutely. He did periodically. Some of them were quite good and some of them not as much.

There was also another document I wanted to share with you. This is from one of his notes. You may have seen this at the exhibition as well. It seems like observational data of a fly responding to toxins. This made me curious, did Drosophila (fruit fly) ever feature within your cone snail project?

It was an aspiration. It never really worked. I can’t remember, but at some point late in the game, we got to pure conopeptides. But whole venoms – it was kind of a mess. So, we had some fun with it, but I think where the project really didn’t make as much progress as it could have been was with physiology. Krishnan was good enough to find pretty good collaborators, a person named Sujit Sikdar and some others in IISc who were good neurophysiologists who would take some of the conotoxins purified and check them on mammalian preps. The fly experiments never did progress. This experiment was inspired by something Toto had done. Toto had found, at that time, that if he [took] different fractions of conopeptides from whatever cone snail he was looking at and injected them into mice, he could trigger very specific and very interesting behaviors in them. Some would go to sleep, some would go around and round, some would hang upside down, I don’t know, they did a whole bunch of things. So, the hope was that maybe we could get some very strange phenotypes with flies as well, but nothing exciting happened very easily.

But the really interesting thing about [the project] was just the whole diversity of people that were involved in it. We had crystallographers, we had really good biochemists, we had people interested in toxins, we had marine biologists, we had evolutionary people. Krishnan involved so many different people and from different parts of the country. It was really a learning experience.

In the papers published from this project, there are mentions of exploring the healing properties of toxins. Where did that inquiry come from?

I think that whenever you’re doing a project, you make up some kind of a potential result that would be super exciting and that is your stated goal. So, the stated goal was absolutely to be able to find potential peptides that had a really good therapeutic effect that would, for instance, stop the feeling of pain. And there was at least one peptide that was identified as a painkiller from cone snails. But because every single cone snail had a completely different set of neuropeptides, the possibility of finding a completely different peptide that had that kind of effect was also an exciting thing. But in reality, it was, you know, just really beautiful biology. All of these strange neuroactive peptides from snails that were killing fish or harpooning them and eating them. The whole space was so interesting that this was really a way to present the general interest of it rather than our personal motivation for the work.

That said, we did actually have some ideas of maybe even starting a company. So, these snails were called vaazhapoo shangu in Tamil Nadu. Shangu is basically a shell and vaazhapoo is a banana flower, because banana flowers are cone shaped. We did have the idea of starting a company called Vazhapoo Therapeutics, but we never did.

The shells are now temporarily housed at the archives reading room and they draw immediate attention from visitors. Partly because of their interesting shape, but it does also make people wonder what’s the science behind it. And as an archivist today, it’s interesting to note all of the things that happened before it came to be displayed with us.

Absolutely. The project, to some extent, spluttered after a point. I mean, every project requires someone who is super committed to doing something. So, I will put my hand up and say that, for instance, if there was going to be… I mean, neurophysiology in the Drosophila neuromuscular junction was something that my lab was doing at that point. But, I didn’t, for some good reasons and some not so good reasons, really say I’m going to take charge of this and every single peptide and figure out what the targets are. I didn’t really push it. Balaram was extremely good at, and really motivated by, finding new peptides with interesting post-translation modifications and trying to find how they have different shapes and so on and looking at a diversity of things. So, characterizing the peptides went really quite well. Collecting the peptides, collecting the cones also went well. But the next step was identifying all of the peptides and what they’re really binding to. Even though we knew what needed to be done, there wasn’t somebody who had the skills and the commitment to push it forward. But the general idea is that you can do biology where you identify things that are really interesting in evolution…

And evolution has figured out so many nice, amazing things to do. In fact, all of molecular biology, all of the enzymes that come out that are used, DNA polymerases, ligases, restriction enzymes, what have you, all of them were invented during evolution. So, you find out interesting things from evolution and then use it for your purposes.

I think the whole chemical ecology project that started later on, which was a big deal for a while in NCBS, as well as some energy for the whole wildlife program in the early days came from this kind of study. And Krishnan, for instance, became, I think, thanks in part to the conotoxin program, very involved with the review groups for the Department of Science and Technology (DST) that were involved in the natural history ecology space. So, he became very well connected around the world and around India. And that also gave the people who were doing wildlife work related things in Bangalore, access and connections to the whole wildlife community across India.

When you visited the archives and looked at the exhibition, you had asked about the purpose of the archive. While we didn’t get to speak about it in detail, I was wondering if you have something to add to that after reflecting on this material.

Krishnan was a very good friend of mine, and I sort of feel very happy to see his [exhibit at the archives]. It’s interesting for all of the reasons that you pointed out, which is, it’s a very unusual sort of interaction with so many different kinds of people and so many different sets of approaches all combined together with a very unusual person in the middle of it. And that’s really good. And also, neither Krishnan nor I, think many good scientists of a particular type, like to follow the pack. We prefer to be in blue water, trying to do something in a unique space, which is not that crowded. So, we get the feeling of doing something that is relatively pioneering that few people are actually doing and thinking about, and we’re learning by doing it. So, I think there was a particular atmosphere there during the time which was fairly special. So, this particular [exhibit], while you don’t articulate the reason, you just know this seems interesting and worth putting there. And I think a couple of other things I saw in the archives were also quite beautiful. It was really nice to [read about] Jamal Ara, who did all of this early bird watching. Everyone thinks that something they’re doing now is incredibly novel, but actually, these ideas and the spirit have been there for a long time. So, it’s nice to see records of inspirational people and events from the past.

This interview has been edited and condensed for clarity. Images sourced from the K S Krishnan Papers should not be confused with the papers of the physicist K S Krishnan, which is also housed at the Archives at NCBS.