What ails biomedical research
Research in health sciences in India is no more oriented towards problem-solving based on years of field work, one of the reasons why many old and new diseases continue to haunt us.
INDIA WAS ONCE A PIONEER IN MEDICAL research. Indian and British stalwarts did excellent plague research (The Great Plague Commission of the 1900s) and malaria research during pre-independence days and the decades immediately following Independence. The Indian Research Fund Association, started in the1900s, was the body in charge of giving grants for medical research. After Independence, this became the Indian Council of Medical Research (ICMR), with Dr C.G. Pandit as its first Director. The first research institute founded in the country was the National Institute of Nutrition in Hyderabad and the second one, started in 1952, was the Virus Research Centre (VRC) in Poona (now Pune). The post of Director of ICMR was upgraded to Director General (D.G.) since several more institutes were started after Independence.
The ICMR has come a long way from the days of Dr C.G. Pandit, who was a great visionary. The tradition of excellence he established continued for many years under some later D.G.S too. There were stalwarts like Dr C. Gopalan, Prof. V. Ramalingaswamy and Dr A.S. Paintal (who retired in 1990). Their stewardships can be said to be the golden era of progress and expansion in research. They were all Fellows of the Royal Society, were eminent scientists of international repute and they focussed on quality research. Many Institutes came up for different specialities such as malaria, filariasis, kala azar, and so on and were doing problem-oriented research work. In course of time, everything petered out into routine research, like it was just a job.
CURRENT RESEARCH
One may ask what present-day bio-medical “research” in India is all about. There are many institutes in many disciplines. There was an interesting incident I would like to quote from my experience when I was the Director of the Vector Control Research Centre in Pondicherry (now Puducherry). Sometime in 1981, the then Prime Minister, Indira Gandhi, asked the then Union Health Minister, B. Shankaranand, what ICMR was all about. A meeting was then organised at the ICMR to which Indira Gandhi was invited. The Directors of different ICMR institutes made audiovisual presentations of the work their institutes were involved in.
Indira Gandhi listened patiently, making notes. She then complimented the scientists for their presentations and thanked the hosts. In the end, she said that she could not understand why there was so much of night blindness in Rajasthan; why so many women suffered from cervical cancer; and why so many people died of malaria and other communicable diseases. She wanted to know what the ICMR has done about them.
It was a revelation to many that the fruits of the research done at the ICMR had not benefited the common man. For many years after Independence, and even some years before, philanthropic foreign organisations such as the Rockefeller Foundation (R.F.) and the Ford Foundation were working in India, the former in the health sector and the latter in the agricultural sector. The VRC was started by the Rockefeller Foundation in collaboration with the ICMR and became world famous for its work on arthropod-transmitted viral diseases.
A mini serological survey done by the VRC for the first time in India in 1949 showed the presence of antibodies to several viral diseases, including Zika, in human sera even at that time. The VRC’S work on Japanese encephalitis (J.e.),and Kyasanur forest disease (KFD) was outstanding in the field of ecology and epidemiology. The Rockefeller Foundation wound up its operations in 1970. The ICMR could not maintain the tempo of work and became a large government organisation.
The important question is whether we have achieved any progress in the control of diseases such as malaria, dengue, chikungunya, Japanese encephalitis, KFD and so on. We are still facing episodes (and epidemics) year after year even now. There are also some neglected tropical diseases (NTD) such as scrub typhus which were totally ignored. Many research institutions were started in different parts of India for bizarre reasons, for example some politician wanted an institute in his constituency or some scientist had to be rewarded with a Director’s post.
Institutes were also created to relocate experienced and qualified scientific personnel displaced because of extraneous reasons, VCRC and Malaria Research Centre (MRC), and sometimes even to accommodate scientists whom the government did not know how to deal with (for example the Centre for Research in Medical Entomology, CRME). Then there were regional aspirations to be satisfied, so there are regional medical research centres. In some institutions, there is obviously a lot of replication of work. There was no more problemoriented research.
The questions Indira Gandhi raised several decades ago seem relevant even now. Many health problems continue to haunt us, some of them new to science such as COVID-19, and we just do not seem to be able to face the situation on a war footing. In my view, the Indian Council of Agricultural Research (ICAR) contributed substantially to the nation through its green revolution (thanks to Prof. M.S. Swaminathan) and white revolution (thanks to Prof. Varghese Kurien). Of course, progress in the field of health is not perceptible and publication of papers in journals is not a solution.
Even now, people continue to suffer/die of malaria, filariasis, kala zar, KFD, and so on all over India. I have written several articles in the Journal of Communicable Diseases and in magazines such as Frontline to highlight the deficiencies in our approach to biomedical research. But no one in authority seems to have taken any cognisance of these.
In the1930s, Hitler’s Germany and Stalin’s Russia prescribed thrust areas in research, damaging science to such an extent that many scientists migrated to other countries. Our present-day situation is similar. The priority areas in biomedical research now get funding only if there are catchy phrases like molecular biology, climate change, and so on. Foreign collaboration has now reached such a ridiculous extent that we have become suppliers of raw material for research (for example human blood samples infected with malaria/filarial parasites) to foreign collaborators for their research work in return for dollar grants and foreign trips. Such foreign collaboration has stifled meaningful indigenous research, and scientific workers, especially those who return to India after higher training abroad, want air-conditioned laboratories and costly imported equipment, and they also want to publish papers which may not have any relevance in solving public health problems.
As far as public health is concerned, the problems are in the field and emphasis should be on working in the field. Unfortunately, it is a fundamental problem in our polity, as in many parts of the world, that science and research are no longer directed towards problem-solving. According to Dr Halfdan T. Mahler, a Director General of the World Health Organisation (WHO), biomedical research is oriented towards palliatives, which continue to attract those who finance research, not towards finding cures. He felt that indigenous planning and working did not suit those who were “market fundamentalists and free trade theologians”.
The government has been liberal with funds. The institutes have huge buildings, costly equipment and are flush with money. Most of them have done almost nothing to contribute to the immediate health needs of the country; and some are just replicating the work of other institutions. But all of them do publish a number of papers in journals. In 1975, Dr Gopalan, D.G., ICMR, started scientific advisory committees (SAC) for each institute. This was meant to have some kind of a performance audit. The SAC of each institute, chaired by the D.G., had several scientists from outside the ICMR with expertise in the disciplines in which the institutes were working. There really was intellectual discussion, and positive directions were given. This system was continued by his successors, Prof. V. Ramalingaswamy and Prof. A.S. Paintal, who even improved upon the system by delegating more decision-making powers.
Nowadays, the D.G. does not attend the SACS of any institute. Scientists from outside the ICMR who have retired are appointed as chairmen. While it is certainly not my intention to downplay the role of outsiders as chairmen of the SACS, many of them are square pegs in round holes. The ICMR sends its own representatives and they speak mechanically about ICMR policies, Five Year Plans, and so on. If you ask them anything more, they say they have no briefing.
A well-known scientist who is no more used to say that the work in most institutes was routine, repetitive, like flogging a dead horse, with no solution being found to the problem at hand. Most of the publications from these institutes are reviews of already published papers. Routinely, recommendations from each institute are made, discussed by an SAC in the ICMR, and then sent to the Health Ministry and ultimately to the government, where they are filed. There is no evaluation of what has been done and whether they are useful to the health needs of the country. Does it indicate progress in biomedical research? Not that there are no problems with particular institutes. They have many constraints. More than 90 per cent of an institute’s budget goes towards meeting salaries. Vacancies in senior positions are never filled. And invariably retired scientists are appointed as consultants. A Director of an institute faces all kinds of problems, both administrative and scientific. If there is an epidemic when lots of people die, like Japanese encephalitis and now COVID-19, they are just not prepared to meet the crises.
SOCIAL VALUE OF RESEARCH
Prof. A.S. Paintal, who retired as D.G., ICMR, in 1990, wanted to introduce a sense of purpose among scientific workers. He was highly critical of assessing the performance of a worker on the basis of the number of publications and their citations. “As a general rule,” he said, “it is quite out of place... it undermines the far more useful work in more urgent fields (such as leprosy, of no value to the West). It is, therefore, only fair that such scientists are assessed on the basis of other criteria such as usefulness of their work to Indian S&T [Science and Technology] and social value. In fact, by a judicious mix of these criteria it should be possible to make a fair judgment about whether the best ‘tomato’ is better than the best ‘potato’... even in the same institute. Such approaches ensure that certain people who have devoted a large part of their time to the development and housekeeping aspects of scientific institutions are not left out in the assessment process.” He even started the Society for Scientific Values. However, his efforts for radical reforms in Indian institutions, as D.G., ICMR, and as president, Indian National Science Academy (INSA), met only with negative response.
FIELD WORK IS VITAL
Thankfully, for diseases such as malaria, which is still prevalent in large tracts of India, the National Vector Borne Disease Control Programme (NVBDCP) shoulders the blame, though the implementation of the control strategy is with the State governments. Japanese encephalitis is one such virus disease which periodically occurs every year in epidemic form following the monsoon season. We just do not have the infrastructure to monitor the vector population density routinely since disease in humans is the result of spillover of the huge mosquito population. They have produced vaccines for Japanese encephalitis and KFD (another virus disease), but their utility is limited because of deficiency in implementation, and they are multi-dose vaccines.
There are not many entomologists available to work in the field. The available few are more keen to do work in laboratories on molecular aspects of entomology and not in the field. This aspect is worrisome for the national programme for diseases control. Even epidemiologists are more wedded to the armchair and would like to solve a problem through computers. This was the major difference when the R.F. was working, where its top scientists, all foreigners, were in the field all the time and shared the hazards with their Indian counterparts in the field. Major advances were made in the understanding of diseases such as Japanese encephalitis and KFD. I was associated with them, living and working in a forest environment for 13 years!
Once the R.F. left, our government should have continued to work on unfinished business, such as the involvement of bats in the natural cycle of KFD. Now, bats are shown to be important in COVID-19. We have lost a lot of time. In KFD, there are three important cycles: the bat-tick-bat cycle; the small mammal-tick-small mammal cycle; and the monkey-tick-man cycle. Whenever an episode of monkey deaths with human disease is reported, as is frequent in pockets throughout the Western Ghats, the institutes rush a team to the spot, do routine studies, but concentrate only on the third aspect, that is, the monkey-tick-man cycle. The first two aspects, which are most important, are totally ignored because this involves intensive field work. They just are not interested in the source of the virus and how it spreads from the original reservoir, bats, to small mammals to the tick population. They publish a quickie and are satisfied. It is
a tragedy that no complete investigation of the disease or the virus is done in any area.
THE CORONOVIRUS PANDEMIC
Now we have the coronavirus, a pandemic that continues to claim thousands of lives all over the world. Who has the responsibility ultimately? The involvement of bats in the natural cycle of a virus (KFD) was published by me as early as 1969. There is no evidence that any serious research work has been undertaken on the reservoir status of bats, particularly since dangerous viruses like Ebola, KFD, and even COVID-19 have been associated with bats. A headline in The Times of India dated July 23, 2019, was frightening: “India Needs to Prepare for Ebola, Other Viral Diseases”. It quoted an article in the Indian Journal of Medical Research: “Bats are thought to be the natural reservoirs of this virus…. India is home to a great diversity of bat species…” But Ebola has not yet come to India, though there is every possibility of it coming, but interest in bats seems to have waned.
Weifeng Shi, a professor at the Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong Province, said that “2019-ncov originated from one source within a very short period and was detected relatively rapidly”. To learn more about the virus’ origins, the researchers compared the SARS-COV-2 genetic sequence with those in a library of viral sequences and found that the most closely related viruses were two coronaviruses that originated in bats, the greater horseshoe bat and Rhinolophus sinicus. One can understand that the health authorities are fully engaged in combating the pandemic. But from a research angle, nothing serious seems to be on the anvil.
ZOONOTIC ASPECTS OF CORONAVIRUS
The BBC environment correspondent reported on July 29 on the work of Prof. David Robertson, of University of Glasgow, who has said that the coronavirus has been circulating among bats for several decades. It is really shocking that there is no evidence of any work being done on the zoonotic aspects of coronavirus, particularly since a related virus, Ebola, has been acknowledged to be associated with bats. With the spread of the new coronavirus in China and the world over, scientists are attempting to find out its origins. However, a recent study shows that bats of the species Rhinolophus sinicus may be the most probable hosts. Since bats were shown to be the carrier of SARS in 2003, not only have many severe acute respiratory syndrome-related coronaviruses (SARSR-COV) been isolated from bats, these mammals have been recognised as the natural reservoir for over 100 other viruses including MERS, the Ebola virus, the Marburg virus, the Hendra virus and the Nipah virus, to name a few.
Why and how are the bats able to carry and spread so many viruses? Wudan Yan noted: 1. Bats’ high-density lifestyle sets up a perfect storm of viral transmission; 2. The tremendous diversity in and among bat species, which accounts for roughly 20 per cent of all mammals; 3. Bats fly far and wide, carrying the viruses to more areas than most mammals; and 4. Immunity and body temperature created by high flight. Shi Zhengli had already implicated bats as a possible reservoir of COVID-19. They have isolated the virus from greater horseshoe bat and Rhinolophus sinicus (Rajagopalan, 2020). There does not seem to be any interest or effort by any research organisation to do any serious long-term study on the zoonotic aspects of the coronavirus.
It is high time that the country’s premier biomedical research organisation, the ICMR, starts detailed and long-term studies on the zoonotic aspects of diseases, including COVID-19. This is essential for the successful development of policies and practices that reduce the probability of future zoonotic emergence, for targeted surveillance and strategic prevention, and, above all, to engage personnel from outside the medical community also, ecologists, wildlife biologists, veterinarians and even management and social scientists, to understand the interface.
In an article dated August 2, The Hindu quotes Nature Microbiology: “The novel coronavirus (Sarscov-2) which has so far infected over 17 million, and killed nearly 7 million across the world, have been circulating unnoticed in bats for decades. Bats have been the primary reservoirs for novel coronavirus. Prof. Satyajit Mayor, Director of the Bangalore-based National Centre for Biological Sciences, says: ‘Many species of bats har
bour several viruses which can cross over to new hosts. When we disrupt habitats, we will face more such threats.’” Why are not the specialists at the National Institute of Virology taking up the study of bats?
Unfortunately, over the years, science administration in India has become skewed. Even now, we tend to copy international organisations like the World Health Organisation (WHO). They are abstract bodies—their scientists are appointed according to country-designated quota. They work by consensus, by voting in committees. Compromises are made. Like the WHO, we also prepare various reports. Basic raw data are collected at the village and block level (the results are often fudged), and these pass through different levels in the hierarchy at the district, the State, and the national level where it is vetted and finally sent to the WHO, where these are sanctified. It is a pity that such data form the basis, usually, for planning control measures in developing countries.
Many multinational drug manufacturers find it easier to test their products in developing countries through the good offices of the WHO. Nature magazine once reported that the WHO was the sales manager of multinational companies. Also vaccine trials, testing of new insecticides, application of new techniques, etc., have a ready organisation to sponsor them in developing countries. Imagine an institute meant for vector research undertaking a long-term hospital-based trials of an anti-filarial drug produced by a multinational company, and which was earlier condemned by Parasitology Today (a British scientific journal) as not only ineffective, but also dangerous. There are now only sponsored research!
Many insecticide companies from abroad get their product tested in India under grants from WHO Pesticide Evaluation Scheme (WHOPES). Effective and well-tested biopesticides produced indigenously find it a herculean task to reach the stage for operational use. They face innumerable hurdles at every stage and nobody at the top level even tries to remove the obstacles. The headquarters of the ICMR looks more like a big administrative office.
INDIA’S PUBLICATION GROWTH RATE
I now refer to a paper, “Status of India in Science and Technology”, that looks at India according to its publications output in the Scopus International Database, 19962006, written by B.M. Gupta and S.M. Dhawan, National Institute of Science, Technology and Developmental Studies. The contents are revealing. Taking only the publications into account, our annual average publication growth rate was 7 per cent compared to 21 per cent for China. India’s national publications’ share in the Physical Sciences, the Life Sciences and the Engineering Sciences has been global average in each discipline. But in Health Sciences, its share was the lowest, much below global average. A detailed study of the data presented showed that there were 35 high productivity institutions in science and technology in India and, regretfully, the ICMR is not one of them. A list of productive Indian scientists showed none from the ICMR.
The authors mentioned 50 papers from India which received higher citations compared with their counterparts under the ICMR. Of these, 28 papers have lead authors from Indian institutions whereas the remaining 22 papers had lead authors from a foreign institute. The Indian institutional participation in these 50 high-cited papers was from 25 organisations (ICMR not mentioned). It makes very sad reading for one who has the interest of ICMR at heart and who had spent a lifetime working with ICMR.
But where are we now? Now the trend is towards project-oriented and paper publishing research and competition at every level and not problem-oriented research. Hard field work has given way to cozy research in air-conditioned laboratories equipped with computers, with readymade, commercially available and easy-to-operate test kits. The emphasis is now on the number of papers one has published, the amount of grants one has generated and the number of Ph.ds one has produced. Everything is time-bound now. No more a sense of adventure or curiosity to find solutions to solving our problems. Have we solved any health problems so far? There is no long-term research anymore. Field work has lost all priority. There are so many restrictions on scientists by a huge number of rules and regulations. How can any work on subjects such as Ecology, Epidemiology, Entomology and Zoonoses be conducted? How can our country ever progress in the area of biomedical research?
There is too much of red tape at every level. Take for example the case of Dr. Shiva Ayyadurai, an Indianamerican scientist, who returned to India, heeding the call given by our Prime Minister to come back to India. He was prevented by the top administrators from doing anything worthwhile. This was widely quoted in Nature and in many foreign publications. He went back to the United States after- knocking his head against the Indian bureaucracy. Hitler’s Germany and Stalin’s Russia saw many scientists escape to freedom to do quality research. This is happening in India.
China is now luring scientists, giving them position and importance. China now leads in areas such as Stem Cell research. One such scientist who returned to China and became Dean of Peking University contrasted China’s “soul searching” with the U.S’ “self satisfaction”. Should India too not “soul search”? The argument that China is totalitarian while we muddle through our democracy is not good enough. We need good leadership, dedication, discipline and determination. Can ICMR emulate premier institutions like the Indian Institute of Science or the Tata Institute of Fundamental Research in quality research?
It is a utopian dream. m Dr P.K. Rajagopalan is former Director, Vector Control Research Centre, Pondicherry, Indian Council of Medical Research.