Nobel laureate Sir Venkataraman Ramakrishnan (he prefers ‘Venki’) is the current president of the British Royal Society, the UK’s premiere scientific institution and the oldest scientific academy in the world. A structural biologist, his work on the structure and function of the ribosome led to a Nobel prize in chemistry in 2009, which he shared with scientists Thomas A. Steitz and Ada Yonath. He is also the author of the recent book, ‘Gene Machine: The Race to Decipher the Secrets of the Ribosome’, an absorbing, accessible account of his academic career and the scientific collaborations that led to the award-winning research on the ribosome, a complex molecule that is at the very centre of what we call ‘life’ as the site of protein synthesis within all living cells. In India to attend to talk about the book and attend literary events such as the Kolkata Literary Meet and the Jaipur Literature Festival, where he delivered the keynote address on Thursday, Sir Venki spoke to Lounge in Bengaluru, which he visits regularly to interact with students and researchers at the Indian Institute of Science (IIsc). Edited excerpts:
You’ve written not only a science book but a very personal book. As a first-time author, how did you decide on the narrative structure of the book?
It could have been either a complete gossip piece or a very science-y piece, but I’ve tried to weave the two together; so it is science but it is also the world of science. As a scientist, you write papers and articles for science journals but they are not the same thing -- since becoming more involved in public engagement (as the president of the Royal Society) I have written op-eds and essays for the general reader. But I think, really, you develop a sense of style by reading. You are what you read and if you read a lot, you subconsciously absorb certain styles. It’s quite controversial now -- but one of the books I read when I was a physics undergraduate in Baroda was The Double Helix by Jim Watson -- a brilliant book because it showed for the very first time what it was like to be in the middle of some exciting experiment, what it was like to go after something, written in a very, very frank manner. Whether you agree with Jim and his characterisations or not, it was a very original book. Before that all science books were somewhat bland -- everything was great, everything was logical -- and here there was this guy stumbling around, making mistakes, kind of being a bit sneaky -- it showed the scientist as a human being. Of course, he also talked about the problem and why it was gripping. It was something of a model, though I don’t talk about people’s appearances or call them ugly or whatever. There’s some gossip in the book but it’s not malicious. And there are still many sentences that make me cringe -- I can’t believe I wrote this really awkward sentence! Of course, it’s too late now.
One of the key insights from your research into the ribosome, its structure and function, was a deeper understanding of how antibiotics work. But as we know, research into new antibiotics is sparse. Is there a real crisis and how do we tackle this?
There hasn’t been a new CLASS of antibiotics for at least 20 years. So it is a real problem, it is a serious problem. And I think while we do need antibiotics we also need to change the practices around them, for example the use of antibiotics in animal husbandry and so on. There’s a big social and technical challenge there, and we do need new antibiotics, but it’s a complex problem. To give you an example, if you know the binding site of an antibiotic you can ask why does the cell acquire resistance to it and then you can develop new compounds that will attack the same target and the same site but will not be susceptible to those resistance mechanisms. That is not easy. You can make a new compound that works well in a test tube or even a cell culture, but getting an antibiotic into a human being is a different set of problems. For many, many inhibitor compounds, maybe thousands, only one makes it as a viable clinical drug. That’s why drug development is so expensive. One reason companies don’t like it is because the money in the antibiotic business is limited. If you generate a third generation antibiotic ideally you need it only for patients who have resistant infections, otherwise why give them a new antibiotic? So the patient pool is small, and if it is good they only need it for a week or so. So we need governments to be involved, we need international organisations like the World Health Organisation or non-profits like the Gates Foundation to step in.
What according to you are the next great frontiers in biology, the big unsolved problems for scientists?
The obvious one is the brain and how it works. Another is stem cell biology -- the ability to regenerate tissue from pluripotent cells, which don’t have to be embryonic cells but can be cells from anywhere in the body. There are now ideas for converting any cell type to any other cell type, but still a lot left to be uncovered. And then, of course, there’s the origin of life and whether there’s life on other planets. How did life evolve from no life, from chemicals? How did the gene itself evolve, or the genetic code -- that’s been around for a long time and we still don’t understand it completely. Some of these questions are hard -- people have been trying to crack the origin of the genetic code for a long time. So many of the big mysteries are still left.
You were a physicist and then you became a structural biologist, and finally you won a Nobel in chemistry. Can you explain how this happened?
Ah, see this is a misconception on the part of the public. These disciplines are not completely separate... there are no hard boundaries or borders between these disciplines. And the fact is that in biology, if you get down to the level of the cell, it is all about molecules, and if you want to understand the molecules you have to study their structure and interactions -- so that becomes chemistry. So a lot of prizes that you would think of as in the field of biochemistry or molecular biology are awarded in chemistry -- there is no biochemistry or molecular biology prize, so the Nobel committee has to decide where to put it. Now they could have put this in physiology and medicine equally, but I think they want to reserve that for things that are less molecular.
‘Intersectionality’ is a big thing in the social sciences. Is it big in science as well?
I don’t quite view it in those terms. Sociologists like to coin all these terms but this is not something new. If you look at the history of the Royal Society when it was founded (in 1660),... you take a guy like Robert Hooke, he made huge discoveries in physics but he also discovered the cell and was the first guy to coin the term ‘cell’. Many of the early scientists couldn’t be defined as this that or the other.These narrow definitions must come from university departments, but it’s not really intrinsic to science. What science needs is simply the breaking down of barriers -- so that if people want to move across departments in search of a problem, it’s seamless. I never consciously moved, except when I went from physics to grad school in biology, but other than that I’ve simply been following a problem and learning the things that I needed to solve that problem. Some of the techniques come from physics -- crystallography is sort of physics -- some of them come from chemistry. You just use what you can to solve the problem. But you’re not thinking ‘oh, I’m using chemistry now’. (laughs)
Now the conversation around genetics is all about gene editing and CRISPR-Cas 9 - its implications and ethics. There is speculation that the technique itself is over-hyped and not safe.What are your thoughts on this?
Any new technique goes through phases -- promise, hype, disillusionment, and then eventually, it actually works and works beyond the hype. You can see that with lots of things-- the internet, microcomputers. But I would say that we are at somewhat of a crossroads here, where we can edit the genomes of animals including ourselves, and this needs to be done fairly carefully. First of all the safety of the method has to be worked out and that requires long-term animal studies and so on. The other thing is, people have to ask when is (using the technique) acceptable -- and that is a social decision rather than a scientific decision. It has to be answered by society. You have to involve the public, lawmakers, governments and get proper regulations. This crazy guy in china -- I wouldn’t be surprised if he ends up in jail because the Chinese are not at all happy about his experiment and being this sort of renegade scientist. Anyway, it was a particularly stupid application of the technique -- we don’t know what the risks of the procedure are and it was used for a potentially small risk. I think people have to decide when it’s worth the risk and this has to be an international consensus -- otherwise people will just go to some country where it is allowed. The ethical questions are complex -- it can be used to cure genetic diseases where there’s a single genetic defect and you can correct the gene in the person, and not necessarily in the germline. But the second way is doing it in the germline and that’s a bit more complicated ethically, because your genome has changed and your offspring is stuck with your decision. Now you could argue that mutations happen all the time and your offspring are stuck with those! So it is not cut and dried -- say there’s a terrible disease and you want to make sure your offspring didn’t have to deal with it, it would be ok IF it was completely safe and predictable. But we’re not sure we are there yet.
The one thing that becomes very clear in your book is that scientific achievement is slow and incremental, and you could work all your life to solve one tiny part of a problem. Given this, how do we get young people interested in research?
It is true but it has always been true. Even in my time, people wanted to get into the IITs... I mean, I might have gone to IITs -- I just didn’t get in! Part of the problem is science careers are risky and don’t pay as well, so the reward isn’t great even if you make it. Ultimately, you have to go because you care about science, you’re curious and you have that burning desire to be a scientist. Luckily, lots of bright people want to go into science, just like luckily lots of young people want to become musicians, though that’s a very hard life as well. Science and music and the arts --they are very creative and risky, but they attract people who say ‘I don’t care about making a lot of money or security, I’m doing it because I’m passionate about it’. So what we have to do it is encourage that passion, nurture it and try and make it better for them. Books like this may help -- they shouldn’t go in with a bogus picture of what it’s like to be a scientist.
Do you feel that we are moving towards a world driven by illogic, emotion, and unreason rather than, as we might have hoped, one driven by rationality and science?
Bertrand Russell called our age the infancy of reason. Rationality has evolved only very recently, and deep down we are very emotional creatures. I talk about that at the very end of the book -- about how we are not willing to accept the fact that science progresses in a messy way. We want to have heroes and villains because we are emotional creatures and we want to interpret everything in terms of a story. I’m pessimistic, but I think we have to keep trying to uphold the vision of rationality as a good way to move forward and scientists can do that by engaging with the public. There does seem to be a worldwide phenomenon of irrationality -- look at Trump, Putin, Brexit. It does seem as if the world is going through some strange phase at the moment, and I think it’s something to do with the inequalities created by globalisation, by technology. People are feeling threatened and insecure and when people are threatened and insecure, they are more susceptible to irrationality.