Interview

The Nobel laureate Venki Ramakrishnan discusses COVID-19, vaccinations, science education in India, among other things

Print edition : August 13, 2021

Venki Ramakrishnan: “The cost of this pandemic is in the trillions of U.S. dollars. India has an extremely low investment in public health infrastructure and needs to increase it manyfold to be ready for future occurrences.” Photo: K. Murali Kumar

A molecular model of a ribosome. Ramakrishnan: “We understand quite a bit about ribosome mechanisms. A lot of focus is now on how ribosomes are controlled and regulated and how the cell deals with problems encountered during translation as a result of stress or infection.” Photo: Getty Images/iStockphoto

Ramakrishnan: “Apart from humanitarian considerations, it is important to vaccinate the entire world because otherwise there will be large reservoirs of SARS-CoV-2 remaining in circulation. This will lead to mutations and new variants which may be worse [than the original virus], including ones that render the current vaccines ineffective.... the only way to bring the virus under control is to suppress it globally, and that means vaccinating globally.” Here, a long queue for the COVID-19 vaccination at a school in Anna Nagar West, Chennai, on July 16. Photo: Pichumani K.

C.V. Raman. “Prior to Independence, India produced several renowned scientists, including... S.N. Bose, Saha, Raman and others.... Since then, although there are several pockets of excellence in India, it has produced too few truly world-class scientists....” Photo: The Hindu Archives

Meghnad Saha. “Prior to Independence, India produced several renowned scientists, including... S.N. Bose, Saha, Raman and others.... Since then, although there are several pockets of excellence in India, it has produced too few truly world-class scientists....” Photo: The Hindu Archives

S.N. Bose. “Prior to Independence, India produced several renowned scientists, including... S.N. Bose, Saha, Raman and others.... Since then, although there are several pockets of excellence in India, it has produced too few truly world-class scientists....” Photo: The Hindu Archives

Ramakrishnan: “So in terms of immediate reach, popular science writing can have a tremendous impact.... Writing for the general public is hard because you have to explain everything from first principles but do it without being condescending.”

Interview with Venki Ramakrishnan, structural biologist and a winner of the 2009 Nobel Prize in Chemistry.

Venki Ramakrishnan is a well-known structural biologist and a Nobel Prize winner. Born in Chidambaram, Tamil Nadu, in 1952, Ramakrishnan graduated in physics from the Maharaja Sayajirao University of Baroda in 1971 and in 1976 received a doctoral degree in the subject from Ohio University in the United States. Although trained in theoretical physics, his interests later shifted to molecular biology, and he conducted postdoctoral research on ribosomes at Yale University in New Haven, Connecticut, the U.S., from 1978 to 1982. He worked as a biophysicist at Brookhaven National Laboratory in New York from 1983 to 1995. In 1999, Ramakrishnan joined the Medical Research Council (MRC) Laboratory of Molecular Biology at the University of Cambridge in England and continues there as a programme leader in the Structural Studies Division.

While at Yale, Ramakrishnan worked in the laboratory of Peter Moore and learned to use the technique of neutron scattering to investigate the structure of a small subunit of the ribosome in the bacterium Escherichia coli. He continued to use neutron scattering for some time but switched to using the high-resolution method of X-ray crystallography to elucidate the atomic structures of ribosomes and other molecules, including chromatin and proteins which are known as histones.

In 2000, Ramakrishnan and his team solved the structure of the 30S ribosomal subunit and its complex with several antibiotics and its mRNA and tRNA ligands. Ramakrishnan, along with Thomas A. Steitz and Ada E. Yonath, won the Nobel Prize in Chemistry in 2009 “for studies on the structure and function of the ribosome”. His research focus now is “on how ribosomes are controlled and regulated, and how the cell deals with problems encountered during translation as a result of stress or infection”.

He was elected as a Fellow of the Royal Society, the world’s oldest independent scientific academy, in 2003 and served as its president from November 2015 to November 2020. Ramakrishnan was elected as a member of the European Molecular Biology Organisation in 2002 and the U.S. National Academy of Sciences in 2004, and as a foreign member of the Indian National Science Academy in 2008.

Ramakrishnan received the Louis-Jeantet Prize for Medicine in 2007 and the Heatley Medal, awarded by the British Biochemical Society, in 2008. He has also received honorary degrees from the M.S. University of Baroda, the University of Utah and the University of Cambridge. He received the Padma Vibhushan, India’s second-highest civilian honour, in 2010. Ramakrishnan was knighted in the 2012 New Year Honours for services to molecular biology by the U.K. government.

Apart from publishing hundreds of academic papers in prestigious journals, Ramakrishnan authored a popular science book, Gene Machine: The Race to Decipher the Secrets of the Ribosome, which came out in 2018, and is currently writing a book with the working title Is Death Necessary? Why and How We Age and Die.

In this exclusive interview, Ramakrishnan speaks on COVID-19 and the need for universal vaccination, the importance of a robust public health system, the chances of the emergence of new viruses, biological warfare, his current research at the MRC, his experience as president of the Royal Society and much more.

The COVID-19 pandemic has still not been brought under control in most parts of the world. Progress in vaccination, which is considered to be the only long-term solution, is varied and uneven among countries. An editorial in The Lancet details the “Rocky road to universal COVID-19 vaccination”. In this context, you call for a global vaccine consortium. Could you please explain the importance of such an initiative?

Apart from humanitarian considerations, it is important to vaccinate the entire world because otherwise there will be large reservoirs of SARS-CoV-2 remaining in circulation. This will lead to mutations and new variants which may be worse [than the original virus], including ones that render the current vaccines ineffective. Such strains could then have the potential to reinfect countries where prevalence is low due to vaccination. Thus, the only way to bring the virus under control is to suppress it globally, and that means vaccinating globally.

You said in an address in 2020: “The current COVID-19 pandemic has had terrible effects and we cannot yet foresee how it will end.” What are your thoughts after one year? India was severely affected by the second wave of the pandemic. How do you look at the COVID-19 situation in India?

Each time we suppress a wave, the virus has emerged with new variants and created subsequent waves. India rather prematurely declared victory over COVID-19 early in 2021 and relaxed restrictions, allowing mass gatherings. The combination of new variants and premature relaxation of control measures led to a massive new wave [and] to thousands of deaths. Moving forward, it is important to maintain transmission control measures while speeding up vaccination until a large majority of the population is vaccinated. Given that the supply of vaccines is limiting, rather than a free-for-all, there should be an orderly process in which priority to various groups is based on risk (for example, based on age, high-risk occupations such as health care professionals or those who come into contact with large numbers of the public). This is the fastest way to reduce hospitalisations and is best coordinated at a national level with the involvement of States.

In an article in The Guardian, you wrote: “We must learn from our successes and failures in this pandemic to be better prepared for the next one.” Many eminent people have blamed the exacerbated impact of the current pandemic on the downgrading of public health systems in many countries. What should constitute better preparation for the next one?

Many countries, including those with leading expertise in public health such as the U.K. and the U.S., were caught flat-footed by the pandemic. This is because governments try to save money on things that are not thought to be imminent, even though pandemics were high on the list of risks in the most knowledgeable countries. The COVID-19 pandemic has taught us that not being prepared for catastrophic occurrences is a false economy. The cost of this pandemic is in the trillions of U.S. dollars. India has an extremely low investment in public health infrastructure and needs to increase it manyfold to be ready for future occurrences. Even in the absence of pandemics and other crises, such investment will pay off by improving the general health of the population and contributing to economic productivity.

Also read: On the political economy of pandemics

In the future, there needs to be better international collaboration on early detection and characterisation of new pathogens and sharing of information about new outbreaks. We need a political environment in which countries where outbreaks begin are not blamed, but rather the outbreak is looked at as a global problem and dealt with collaboratively. This is best done through international agencies, including the WHO [World Health Organisation], which should be autonomous and insulated from political pressures as well as have real powers, similar to [those] international nuclear materials inspectors [have].

Epidemiologists such as Rob Wallace were warning about the threat of deadly pathogens such as SARS-CoV-2 at least from the turn of this century. Against the background of the current pandemic, you warn that “it is completely predictable that an even worse virus will emerge someday”. Why? Could you provide a glimpse of the evolutionary trajectories of influenza viruses?

The emergence of new viruses, including potentially deadly ones, has probably been going on throughout history. Until a few decades ago, most new outbreaks would simply be contained in the village where they occurred because people were not particularly mobile, and would never even be recognised let alone characterised. With urbanisation and globalisation, viruses that jump hosts into humans have a much greater chance to spread, thereby dramatically increasing the chances of a pandemic. Humans and animals have also come into closer contact due to the explosion in the human population as well as the loss of native habitat for many wild animals. Some practices such as exotic animal markets can also exacerbate the problem. It is very likely that new viruses, possibly ones that are more lethal than SARS-CoV-2, will emerge in the foreseeable future.

It is a reality that even after 40 years, there is still no vaccine for AIDS (acquired immune deficiency syndrome) and many other viral diseases. You have emphasised that “it is important to put strong efforts into new and repurposed drugs to combat infection”. Actually, what are the bottlenecks?

I must admit that I did not foresee how effective the first generation of COVID-19 vaccines would be. It is a real tribute to the efforts of many scientific teams, some developing new technologies over the last decades that have borne fruit. However, there will be some [people] who get the disease in spite of being vaccinated, and many others who simply did not have the chance to be vaccinated. It is also possible that new strains may emerge that render the vaccines less effective. It is therefore important to also develop drugs that can be used to treat infections. Some drugs are monoclonal antibodies against viral proteins that bind to the virus and prevent it from infecting. Others are small molecules that prevent the virus from replicating or processing its own proteins (for example, by inhibiting the viral polymerase or proteases), similar in principle to the drugs against HIV [human immunodeficiency virus].

Also read: COVID-19 vaccines developed quickly — is an HIV vaccine next?

The study and development of antibiotics seem to be still in their adolescence, as you have said many times. Another problem with antibiotics research is that “it will not be a lifelong drug”. So, as you interestingly pointed out, “The ideal patient for a pharmaceutical company is a diabetic with high blood pressure and cholesterol and possibly with impotence as well.” Here profit-making calculations assume primary importance. Is this not the case with developing vaccines for viral diseases? What is the importance of government or public intervention in this context?

The economic cost of the pandemic has been huge. If there were to be future large outbreaks of bacterial infections that are resistant to current antibiotics, that too would have large health and economic costs. So the cost to governments of investing in these technologies is very small relative to the potential benefits. Even though COVID-19 vaccines were developed in private companies, not only were they based on decades of public investment in basic research, but even in this case, governments not only funded the development of vaccines by large direct investments but also made guaranteed offers of purchasing large amounts. That is in the middle of a huge and present pandemic. Unfortunately, it is unlikely that private companies can take the long view to develop treatments to avoid unpredictable disasters in the future. It is only governments or international organisations that can take the long view. It is worth remembering that penicillin was first developed as a clinically useful antibiotic by massive government investment in a team at Oxford in response to another crisis: soldiers dying in [the Second] World War of infection. Why wait for the next crisis before acting when it is bound to come sooner or later?

More than a decade has passed since you got the Nobel Prize for “having shown how the ribosome looks and how it functions at the atomic level”. Your research on ribosomes assumes significance now as it will help in the development of better antibiotics. It will also address the problem of antibiotic resistance. How do you view the progress in this direction on the basis of your research?

Many companies did develop new compounds based on the structures with potentially useful properties. However, to develop these compounds into clinically useful drugs is a long and very expensive process that combines iterative medicinal chemistry with assays in cell culture and in animals, followed by clinical trials in humans. The problem has really been that, as we discussed just above, private pharmaceutical companies have generally been unwilling to invest in this, and it is again a case for governments, possibly working together internationally, to make these investments.

In 2020, you completed five years as president of the Royal Society. Could you please share with us your experience with this great body of science and also was that a five-year break from the MRC laboratory?

Firstly, I question your term “five-year break”. The Royal Society presidency is an honorary and allegedly part-time position, so throughout my term I have been a full-time employee of the MRC and kept running my lab in Cambridge.

I came to Britain in my late forties and spent all my time in the confines of the MRC Laboratory of Molecular Biology in Cambridge. So I was rather surprised to be elected as president of the Royal Society in 2015 because prior to that I was entirely focussed on my own research and neither had a network of connections in the U.K. science and political establishment nor broad leadership experience in running organisations or institutions. I accepted the challenge, and my original goals, such as more public engagement, improving education, international relations, etc., were quickly overtaken by two events: Brexit and, in my last year, the COVID-19 pandemic. For the first, the priority was to minimise the damage that would come from disruption of our ties to the rest of Europe and to ensure that scientific collaboration through joint programmes and funding schemes would continue. In this, I think we were fairly successful. In my last year, the Royal Society was also involved in helping to provide scientific advice on the pandemic in a scenario in which our understanding kept changing rapidly as facts emerged.

What is your current research work on, and what problems are you striving to solve today?

The basic structures of ribosomes from bacteria, humans and mitochondria (organelles in our cells that have their own ribosomes) have now all been solved. We understand quite a bit about ribosome mechanisms. A lot of focus is now on how ribosomes are controlled and regulated and how the cell deals with problems encountered during translation as a result of stress or infection. Much of this happens in the so-called initiation phase, a process that leads to ribosomes starting at the correct point on the mRNA containing the genetic message. A year ago, I would have had to explain what mRNA was, but now thanks to COVID-19 vaccines, it is no longer an obscure molecule to the public.

Also read: COVID and other diseases: An Animal Farm perspective

Even today there are a number of people who deny or give less importance to the phenomenon of climate change. But you warn that “the slow-motion ongoing mega-crises of climate change and biodiversity loss, which unmitigated, will be catastrophic for the future of humanity”. As a scientist, how do you assess the gravity of the threat, especially for countries such as India? What can be done to mitigate the crisis?

Just as governments were not willing to put in the expense and effort to be resilient against future pandemics, I fear that they will also not take the measures necessary to act against climate change and biodiversity loss. Moreover, unlike the spread of infections, which at least theoretically could be controlled by closing off borders as New Zealand and some countries did, climate change cannot be dealt with on a country-by-country basis. It will require international agreement and a willingness on the part of wealthier countries to subsidise measures for the common good of the planet. I am not at all optimistic this will happen. There is no law saying that species act in their best interests nor is there any law saying that species will survive forever. On the contrary, the one thing we do know is that species become extinct all the time. It would be a pity, though, if we knew the dangers ahead and did nothing.

You believe that scientists have a social responsibility. In your view what is that responsibility?

Scientists are largely funded by the taxpaying public, at least for a large part of their education and training. So we owe it to the public to explain what we are doing with their money. This means public engagement and a willingness to share information that we acquire. However, there are all kinds of scientists. Some simply like doing their science and don’t want to be bothered with anything else. Some are not very good communicators but are outstanding scientists. Others are perhaps not the most original or brilliant scientists but are excellent speakers or educators or writers. So I am not sure we should impose too many rules on individual scientists, but we should expect broad accountability from the scientific enterprise as a whole.

While talking about making the Indian education system world class in terms of quality, you have suggested a balance between research and education. What are the drawbacks you see in the Indian education system in this regard at this moment?

Scientific research is not fashionable in India. Aspiring parents want their children to be economically secure and prosperous and push them to become doctors or engineers. Actually, doctors and engineers would be extremely beneficial for a country like India, but many engineering graduates never actually practise engineering; they go on to do an MBA and become corporate executives! As in many other countries, education in India is heavily focussed on major exams, with an emphasis on rote learning. It is important for students to understand both science and mathematics as a process of discovery and for undergraduates to get hands-on experience at doing experiments and research projects (possibly by doing summer internships).

India will celebrate 75 years of Independence next year. How do you look at and evaluate scientific research in India in the last seven decades? What are the changes you wish to see with respect to scientific research from policymakers?

At Independence, India had a number of universities which were also leading centres of research. Gradually, however, the centres of research shifted from universities to national research institutes, leaving students, especially undergraduates, isolated from the research enterprise. This is being reversed through the establishment of IISERs [Indian Institutes of Science Education and Research], for which C.N.R. Rao should get credit.

Prior to Independence, India produced several renowned scientists, including J.C. [Bose], S.N. Bose, [Meghnad] Saha, [C.V.] Raman and others. In the early years after Independence, there was G.N. Ramachandran. Since then, although there are several pockets of excellence in India, it has produced too few truly world-class scientists who are perceived as leaders in their field. Many are doing excellent work, but it is often a continuation of what they did as postdocs or graduate students or incremental work that adds to what has been pioneered in the West. Considering India’s population and talent, this is a shame and suggests something is wrong with the research environment. It means that either it is badly underfunded, or there is too much stifling bureaucracy, or the system or culture does not encourage risk-taking.

Also read: Protein machinery

A separate issue is the translation of basic research into entrepreneurship. This too requires a culture of risk-taking, and the problem is a general one not just limited to India. Finally, Indian investment in research is very low compared to the OECD [Organisation for Economic Cooperation and Development] average. But private investment in India is even lower. In most advanced countries, the ratio of private to public investment is 2:1 or higher. In India it is the opposite. So a major problem is low private investment in research, which is related to the problem of translation and entrepreneurship. Many Indians or people of Indian origin have flourished as entrepreneurs in the West. So it is really a problem of the prevailing culture and providing proper incentives that encourage risk-taking and protect risk-takers who fail. Countries like China, South Korea and Singapore have all made far greater public and private investment than India and also made tremendous strides in encouraging entrepreneurship. If India wants to remain at all competitive in the 21st century, it needs to match their ambition and investment.

You advocate for borderless science. But scientific research often develops under a nationalistic spirit. One saw that even with the development of the COVID-19 vaccines. What is the relevance of borderless science in a world where countries compete with one another to achieve more advancement in science?

Science has always involved a mixture of competition and cooperation. Sometimes we can collaborate and also have friendly rivalry, often at the same time. It is not that different from other human interactions, including business and sports. However, there is really no reason for science to be nationalistic. Scientists are advancing knowledge which then becomes the property of all of humanity, not playing for their country like a cricket team.

Moreover, some problems will require sharing resources and knowledge to make headway on a problem. Although there was competition among companies in vaccine development, for many other aspects of the pandemic there has never been so much collaboration and open sharing of data. In facing big future challenges like climate change, biodiversity [and] sustainability of oceans, there is simply no alternative to international collaboration.

Natural origin of virus

Some people have alleged that the coronavirus is a Chinese biological weapon targeting Western or opponent countries. How do you look at it? From a science point of view, what are the chances of using “biological warfare” today?

Very few people (mostly right-wing conspiracy theorists) think that SARS-CoV-2 is a deliberately engineered biological weapon. There is a small possibility that it was the result of an accidental laboratory leak from legitimate efforts to collect and study coronaviruses, including possibly modifying them to study function. Lab leaks have occasionally occurred in the past in labs all over the world. Although there has been increasing concern of a possible lab leak in Wuhan, the majority of scientists still think the most likely scenario is that like other viruses such as SARS [severe acute respiratory syndrome] and Ebola, SARS-CoV-2 has a natural origin. One should remember it took over a decade to establish the route by which SARS became established as a human pathogen, and we still do not know the original source of Ebola. Four decades ago, there was similar uncertainty about the origins of HIV. So these things take time to establish. It is not helped by the fact that relations between China and the U.S. are at a low, with mutual suspicion on both sides.

Virologists are generally in favour of allowing so-called “gain of function” research, which involves modifying viruses to see what makes them more infectious or lethal. Such an understanding can provide clues about how natural viruses can evolve into more dangerous ones as well as provide clues on how to prevent infection. However, the potential benefits of these experiments must be balanced against the risks. Scientists are in agreement that such experiments should be very rigorously reviewed before permission is granted, and they need to be carried out under strictly controlled conditions with regular inspections. Enforcing this internationally will be problematic.

Also read: The controversy being created about the origins of the virus that causes COVID-19

The possibility of developing biological weapons is very real, even, for example, resurrecting eradicated diseases like smallpox or the 1918 strain of flu. Moreover, they do not require large-scale facilities like those for nuclear weapons that could be more easily detected. Ideally, experiments on dangerous pathogens should be subject to international agreements that have teeth, such as countries having their facilities open to international inspectors (again using nuclear materials as an example). I am pessimistic given today’s geopolitical climate that this will happen.

Alexander Gann at the Cold Spring Harbor Laboratory in New York encouraged you to write a book instead of writing a paper for the journal Nature so that you would reach the public rather than those in the scientific community. Thereafter, you wrote “Gene Machine. How important is it for scientists’ writings to reach the general public instead of being limited to the scientific community? How hard was it, in terms of getting your ideas across, to present your book to the general public?

I believe that what Alex said was that only a few dozen people would actually read yet another paper of mine, but tens of thousands would read a popular book. That indeed turned out to be the case for Gene Machine. So in terms of immediate reach, popular science writing can have a tremendous impact. Since science is something the public funds through taxes, it is our duty to share with the public some of the excitement of not only the actual science but how it is done and its history. It is also a way to excite and inspire young people, many of whom may go on to careers in science. Most of us who became scientists were influenced by interesting books we read as children or young adults. Writing for the general public is hard because you have to explain everything from first principles but do it without being condescending. As the physicist Leo Szilard told a biologist who was about to explain something to him: “You may assume infinite ignorance and unlimited intelligence.” It is good advice, and I am taking it to heart while working on my next book, with the working title Is Death Necessary? Why and How We Age and Die.

Jipson John and Jitheesh P. M. contribute to The Hindu, The Caravan and Monthly Review. They can be reached at jipsonjohn10@gmail.com and jitheeshpm91@gmail.com.

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