Will India ever get Nobel for medicine?
We need to take clinical research forward
We,
in India, are obssessed with comparisons with China, especially when it comes
to economic growth. What about the intellectual growth that fuels economic
growth? Now that a Chinese scientist, Tu Youyou, has shared the Nobel Prize in
medicine, 2015, should we not ask ourselves why is it that only one Indian, and
three persons who were of Indian birth and origin but who subsequently acquired
foreign citizenship, have won the Nobel prize in science. There are lessons for
India in the Chinese scientist’s recognition. Tu Youyou was tasked by Mao
Zedong in 1969 to find a cure for malaria that was infesting the Red Army, when
China was in the grip of the cultural revolution, with universities and schools
across the country shutting their doors as the red guards ran riot. After long
research, using her knowledge of ancient Chinese text and clinical tests, she
created a drug based on her discovery of artemisinin, that helped slash malaria
mortality rates in Africa and Asia, saving millions of lives.
The writing is clear on the wall. Money, patience and determination are needed to promote research in the country, especially in issues vital to nation’s health. Further, instead of wasting time on extreme claims for either traditional or clinical research, both can complement each other if we use scientifc methods.
The Indian pharmaceutical industry is the third largest in the world and is ranked world class in terms of technology, quality and range of medicines manufactured.
From simple headache pills to sophisticated antibiotics and complex cardiac compounds, almost every type of medicine is now made indigenously. The industry today can boast of producing the entire range of pharmaceutical formulations — medicines ready for consumption by patients and about 350 bulk drugs, ie, chemicals having therapeutic value and used for production of pharmaceutical formulations. Technologically strong and self-reliant, pharmaceuticals industry has low costs of production and an increasing balance of trade.
Through the introduction of a system of product patents since 2005, it has become a worldwide exporter of high quality generic drugs. India exports pharmaceuticals to many countries across the world, including the US, Germany, France, Russia and the UK.
India is the world’s largest exporter of generic medicines, especially in critical areas like HIV/AIDS and lifesaving vaccines. In the area of clinical work, patient care for instance, India is recognised as a leading country and, at many places in the country, patient care being offered matches the best in the world, at a cost lower than in the developed nations.
This is making India a hub for medical tourism with patients from all across the world coming to India for treatment. Recently, in an an international summit on medical value travel, commerce secretary Rita Teaotia said that the government is making an effort to promote India as a premier global healthcare destination and to enable streamlined medical services exports from India, which is a unique conglomeration of the 5T’s — talent, tradition, technology, tourism and trade.
The total turnover of pharmaceutical industry is estimated at $21.04 billion, of which about 65 per cent is from exports. It spends around 18 per cent of this revenue on research and development (R&D) activities. Low R&D costs, innovative scientific manpower, and a network of national laboratories have enabled research to find simple, cost effective solutions within the reach of a common person, often eliminating the necessity to get hospitalised or undergo serious medical interventions. Consider the case of critical nutrition deficiencies. Iodine deficiency disorder constitutes factor responsible for nutritional deficiencies. Studies conducted in Sikkim and the Himalayan regions in the 1950s and 1960s conclusively proved that iodised salt significantly reduced the incidence of iodine deficiency disorders. The neatly packed commercially available iodised salt has been possible because of this research and if a small pinch can keep iodine deficiency at bay, we have our researchers to thank for.
Likewise, a large number of infectious disorders are treatable now because of indigenous research. Take the once dreaded cholera. One of the most important contributions from India is the discovery of cholera toxin by Sambhu Nath De, which found mention in the prestigious international journal Nature, and of which, the noble laureate professor Joshua Lederberg said: “De’s clinical observations led him to the bold thought that dehydration was a sufficient cause of pathology of cholera, that the cholera toxin can kill ‘merely’ by stimulating the secretion of water into the bowel”. De’s research became the basis for the most important life-saving recommendation in diarrhoea: use of oral rehydration therapy (ORT). Ironically, the seminal research contributions of De done entirely in India were first recognised abroad, after which the Indian medical community promptly praised him to the skies. We still do not have adequate systems of recognising and rewarding excellence. Subsequently, at the National Institute of Cholera & Enteric Diseases (NICED), Kolkata, a new toxigenic strain of vibrio cholera, V cholera 0139, was detected and characterised. NICED has been designated as the WHO collaborating centre for research and training in diarrhoeal diseases in 1980. Besides demonstration of the role of oral rehydration therapy, NICED research also showed that common household drinks (nimbupani, coconut water and rice water) are as good as oral rehydration solutions (ORS) in preventing diarrhea-related mortality and are more palatable.
In 1956, the TB Chemotherapy Centre, later re-named the TB Research Centre (TRC) was established in Chennai under ICMR, with the assistance of the British Medical Research Council, WHO and the government of India. The centre conducted a series of studies on the feasibility and effectiveness of mass ambulatory chemotherapy and showed that home-based treatment of tuberculosis was as successful as hospital treatment, greatly reducing costs. The TRC also showed that supervised administration of anti-TB drugs twice weekly was as efficacious as daily self-administered treatment — this is now known as the directly observed treatment short course (DOTS), which is now accepted worldwide. This research was instrumental in establishing DOTS and short course chemotherapy (SCC) although this happened several years later.
Another success story has been the near-eradication of polio in India. This was a result of the pulse polio campaign of the Indian government. Started in 1995-96, it aimed to cover all children under the age of five years by administering the polio vaccine. This project also included WHO participation besides several other international organisations, state governments and NGOs. One of the landmark studies that showed, for the first time, that pulse polio immunisation can be a useful strategy was done in Vellore, India.
This was also not recognised initially. It also showed the power of mass communication and the fact that effectively imparted information and education is the key to improving health standards in a country, particularly one with low literacy and inadequate access to medical resources.
Indigenous research has also helped to identify problems peculiar to India, though often this is not well known. For example, a new blood group, the Bombay blood group was discovered by the Institute of Immunohaema-tology, Mumbai. The difficulty with this phenotype was that the individual with this blood group can only receive blood from an individual of Bombay phenotype. Although rare in general population, the incidence of Bombay phenotype is quite high in certain tribes — for instance, the incidence is 1 in 33 among the Kutia Kondh tribe, 1 in 127 among Kondh tribe and 1 in 1,244 among the tribal populations of Odisha. It is likely that this high incidence is due to the practice of endogamy in these populations. Similarly, it was earlier believed that glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in India is of the Mediterranean type. However, Indian research has shown that G-6-PD deficiency is heterogeneous, and two new G-6-PD variants namely G-6-PD Rohini and G-6-PD Jamnagar were also discovered. Its importance is in the treatment of malaria with certain antimalarial drugs has been recognised.
India has also contributed significantly to the treatment of diseases that earlier stigmatised the patient and excluded her from society. Leprosy is an example. The major Indian contribution in leprosy has been devising therapeutic regimens. These include pulsed refampicin, a new regimen comprising conventional multidrug therapy (MDT) together with newer drugs like ofloxacin and minocycline shown to be safe and well tolerated, and single dose of rifampicin, ofloxacin and minocycline (ROM) was shown to be as effective as six months of multi-drug therapy (MDT) for patients with mono lesion leprosy. The Central JALMA Institute for Leprosy, Agra, has been instrumental in conducting most of these studies.
There are notable contributions in the biomedical field such as the development of indigenous tilting disc heart valve (Chitra valve) by professor Valiathan. Other distinguished names of eminent scientists who migrated abroad and excelled in research include Hargobind Khurana who received the Noble Prize for Medicine & Physiology in 1968 for cracking the genetic code. Venkataraman Ramakrishna also shared the Noble Prize in 2009 for his work on ribosomes. This shows that high impact research has been done by Indians while working abroad. If India could have retained its medical research talent in India, the Nobel Prize would have come to it.
Several factors, however, inihibit optimisation of our research talent within the country. The state of medical research in a majority of medical colleges has been pathetic and data shows that many medical colleges have not published a single paper in a year. The standard of research publications is also often questionable, with negligible impact factor of journal in which these publications have been published. It is not encouraging to note that 90 per cent of the publications in leading medical institutes have less that 25 citations and less than 0.5 per cent have more than 100 citation. Most of the research publications have been a follow up of the ongoing research work going in the USA and Europe.
We have become a good lab for research by multinational firms. The Indian government allows 100 per cent FDI under the automatic route in the drugs and pharmaceuticals sector.
Department of industrial policy and promotion (DIPP) data suggests that the drugs and pharmaceuticals sector has attracted an impressive level of FDI worth $1,882.76 million during April 2000 to March 2011. Industrial licences are not required in India for most of the drugs and pharmaceutical products. Manufacturers are free to produce any drug duly approved by the Drug Control Authority.
This patent regime has led to the investment from many pharmaceutical multinationals in India. Now they are looking at India not only for its traditional strengths in contract manufacturing but also as a highly attractive location for research and development, particularly in the conduct of clinical trials and other services. Indian and foreign companies are continuing with patented drug launches in India and between 2005 and 2010, the Indian patent office has granted 3,488 product patents, as per a KPMG report. However, this also means that Indian companies that achieved their status in the domestic market by breaking product patents, may in the next few years, lose almost $650 million of the local generics market to patent-holders.
To survive in the global market, it becomes imperative that we turn to research with new vigour. We have not contributed prolifically towards the development of new drugs or new medical equipment. Nor have we developed software of medical importance that has gained worldwide acceptance. Prime minister Narendra Modi recently expressed concern over this state of affairs when at the 42nd convocation of All India Institute of Medical Sciences, he said that India is lagging behind in the field of medical research and more work should be done. He exhorted focus on case history,and said that our research ‘can be a big contribution to humankind’.
There is a desperate need to strenghten medical research in the country. Improving infrastructure is first priority alongwith creating an enabling environment and incentives for research.
Training in research methodology can go a long way. At present, no structured training of research methodology is taught in medical colleges. As a result of inadequate training, students are unable to properly and critically analyse and plan research work. Exposure to research in initial stages of their careers can stimulate some medical professionals to undertake research as a major area of involvement. Though every medical postgraduate has to write a thesis/dissertation at present, the quality of their works is often far below standard and hardly worth publishing.
Many physicians and scientists turn into active researchers by virtue of their aptitude or simply due to an overpowering spirit of enquiry. Robert Koch initially a physician went to discover the TB bacillus and Louis Pasteur originally a chemist became the father of vaccinology. In modern times, the concept of bench to bedside, translational science, has brought the integration of laboratory experience to medical practice in a more organised way. But there are disconnects, in India, between the clinician and the scientist, between MD/DM and PhDs. This gulf between basic scientists and clinicians spawns a fair amount of meaningless research. A close physician-scientist interaction is very important to promote translational medical research.
Medical colleges should be ecouraged to foster relations with various research institutes such as ICMR, DST, CSIR and DBT and universities and vice versa. This would help in the collaboration between basic and clinical research and their learning from each other’s expertise and thus enhance opportunities for translational research.
The industry should also devote resources for research particularly within the field of biomedical sciences. Even after increased investment, market leaders such as Ranbaxy and Dr Reddy’s Laboratories spent only 5–10 per cent of their revenues on R&D, lagging behind western pharmaceuticals like Pfizer, whose research budget last year was greater than the combined revenues of the entire Indian pharmaceutical industry.
India has great potential for clinical research with its large number of patients and availability of most disease categories. The right environment and encouragement would help to promote the quality of medical research. With our intellectual strength, it is time for us to be a global player in contributing to the field of medical research.
(The writer is chairman, cardiology department, Max Healthcare Institute, New Delhi, former head, cardiology department AIIMS,
New Delhi, former director and head of cardiology PGIMER, Chandigarh)
The writing is clear on the wall. Money, patience and determination are needed to promote research in the country, especially in issues vital to nation’s health. Further, instead of wasting time on extreme claims for either traditional or clinical research, both can complement each other if we use scientifc methods.
The Indian pharmaceutical industry is the third largest in the world and is ranked world class in terms of technology, quality and range of medicines manufactured.
From simple headache pills to sophisticated antibiotics and complex cardiac compounds, almost every type of medicine is now made indigenously. The industry today can boast of producing the entire range of pharmaceutical formulations — medicines ready for consumption by patients and about 350 bulk drugs, ie, chemicals having therapeutic value and used for production of pharmaceutical formulations. Technologically strong and self-reliant, pharmaceuticals industry has low costs of production and an increasing balance of trade.
Through the introduction of a system of product patents since 2005, it has become a worldwide exporter of high quality generic drugs. India exports pharmaceuticals to many countries across the world, including the US, Germany, France, Russia and the UK.
India is the world’s largest exporter of generic medicines, especially in critical areas like HIV/AIDS and lifesaving vaccines. In the area of clinical work, patient care for instance, India is recognised as a leading country and, at many places in the country, patient care being offered matches the best in the world, at a cost lower than in the developed nations.
This is making India a hub for medical tourism with patients from all across the world coming to India for treatment. Recently, in an an international summit on medical value travel, commerce secretary Rita Teaotia said that the government is making an effort to promote India as a premier global healthcare destination and to enable streamlined medical services exports from India, which is a unique conglomeration of the 5T’s — talent, tradition, technology, tourism and trade.
The total turnover of pharmaceutical industry is estimated at $21.04 billion, of which about 65 per cent is from exports. It spends around 18 per cent of this revenue on research and development (R&D) activities. Low R&D costs, innovative scientific manpower, and a network of national laboratories have enabled research to find simple, cost effective solutions within the reach of a common person, often eliminating the necessity to get hospitalised or undergo serious medical interventions. Consider the case of critical nutrition deficiencies. Iodine deficiency disorder constitutes factor responsible for nutritional deficiencies. Studies conducted in Sikkim and the Himalayan regions in the 1950s and 1960s conclusively proved that iodised salt significantly reduced the incidence of iodine deficiency disorders. The neatly packed commercially available iodised salt has been possible because of this research and if a small pinch can keep iodine deficiency at bay, we have our researchers to thank for.
Likewise, a large number of infectious disorders are treatable now because of indigenous research. Take the once dreaded cholera. One of the most important contributions from India is the discovery of cholera toxin by Sambhu Nath De, which found mention in the prestigious international journal Nature, and of which, the noble laureate professor Joshua Lederberg said: “De’s clinical observations led him to the bold thought that dehydration was a sufficient cause of pathology of cholera, that the cholera toxin can kill ‘merely’ by stimulating the secretion of water into the bowel”. De’s research became the basis for the most important life-saving recommendation in diarrhoea: use of oral rehydration therapy (ORT). Ironically, the seminal research contributions of De done entirely in India were first recognised abroad, after which the Indian medical community promptly praised him to the skies. We still do not have adequate systems of recognising and rewarding excellence. Subsequently, at the National Institute of Cholera & Enteric Diseases (NICED), Kolkata, a new toxigenic strain of vibrio cholera, V cholera 0139, was detected and characterised. NICED has been designated as the WHO collaborating centre for research and training in diarrhoeal diseases in 1980. Besides demonstration of the role of oral rehydration therapy, NICED research also showed that common household drinks (nimbupani, coconut water and rice water) are as good as oral rehydration solutions (ORS) in preventing diarrhea-related mortality and are more palatable.
In 1956, the TB Chemotherapy Centre, later re-named the TB Research Centre (TRC) was established in Chennai under ICMR, with the assistance of the British Medical Research Council, WHO and the government of India. The centre conducted a series of studies on the feasibility and effectiveness of mass ambulatory chemotherapy and showed that home-based treatment of tuberculosis was as successful as hospital treatment, greatly reducing costs. The TRC also showed that supervised administration of anti-TB drugs twice weekly was as efficacious as daily self-administered treatment — this is now known as the directly observed treatment short course (DOTS), which is now accepted worldwide. This research was instrumental in establishing DOTS and short course chemotherapy (SCC) although this happened several years later.
Another success story has been the near-eradication of polio in India. This was a result of the pulse polio campaign of the Indian government. Started in 1995-96, it aimed to cover all children under the age of five years by administering the polio vaccine. This project also included WHO participation besides several other international organisations, state governments and NGOs. One of the landmark studies that showed, for the first time, that pulse polio immunisation can be a useful strategy was done in Vellore, India.
This was also not recognised initially. It also showed the power of mass communication and the fact that effectively imparted information and education is the key to improving health standards in a country, particularly one with low literacy and inadequate access to medical resources.
Indigenous research has also helped to identify problems peculiar to India, though often this is not well known. For example, a new blood group, the Bombay blood group was discovered by the Institute of Immunohaema-tology, Mumbai. The difficulty with this phenotype was that the individual with this blood group can only receive blood from an individual of Bombay phenotype. Although rare in general population, the incidence of Bombay phenotype is quite high in certain tribes — for instance, the incidence is 1 in 33 among the Kutia Kondh tribe, 1 in 127 among Kondh tribe and 1 in 1,244 among the tribal populations of Odisha. It is likely that this high incidence is due to the practice of endogamy in these populations. Similarly, it was earlier believed that glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in India is of the Mediterranean type. However, Indian research has shown that G-6-PD deficiency is heterogeneous, and two new G-6-PD variants namely G-6-PD Rohini and G-6-PD Jamnagar were also discovered. Its importance is in the treatment of malaria with certain antimalarial drugs has been recognised.
India has also contributed significantly to the treatment of diseases that earlier stigmatised the patient and excluded her from society. Leprosy is an example. The major Indian contribution in leprosy has been devising therapeutic regimens. These include pulsed refampicin, a new regimen comprising conventional multidrug therapy (MDT) together with newer drugs like ofloxacin and minocycline shown to be safe and well tolerated, and single dose of rifampicin, ofloxacin and minocycline (ROM) was shown to be as effective as six months of multi-drug therapy (MDT) for patients with mono lesion leprosy. The Central JALMA Institute for Leprosy, Agra, has been instrumental in conducting most of these studies.
There are notable contributions in the biomedical field such as the development of indigenous tilting disc heart valve (Chitra valve) by professor Valiathan. Other distinguished names of eminent scientists who migrated abroad and excelled in research include Hargobind Khurana who received the Noble Prize for Medicine & Physiology in 1968 for cracking the genetic code. Venkataraman Ramakrishna also shared the Noble Prize in 2009 for his work on ribosomes. This shows that high impact research has been done by Indians while working abroad. If India could have retained its medical research talent in India, the Nobel Prize would have come to it.
Several factors, however, inihibit optimisation of our research talent within the country. The state of medical research in a majority of medical colleges has been pathetic and data shows that many medical colleges have not published a single paper in a year. The standard of research publications is also often questionable, with negligible impact factor of journal in which these publications have been published. It is not encouraging to note that 90 per cent of the publications in leading medical institutes have less that 25 citations and less than 0.5 per cent have more than 100 citation. Most of the research publications have been a follow up of the ongoing research work going in the USA and Europe.
We have become a good lab for research by multinational firms. The Indian government allows 100 per cent FDI under the automatic route in the drugs and pharmaceuticals sector.
Department of industrial policy and promotion (DIPP) data suggests that the drugs and pharmaceuticals sector has attracted an impressive level of FDI worth $1,882.76 million during April 2000 to March 2011. Industrial licences are not required in India for most of the drugs and pharmaceutical products. Manufacturers are free to produce any drug duly approved by the Drug Control Authority.
This patent regime has led to the investment from many pharmaceutical multinationals in India. Now they are looking at India not only for its traditional strengths in contract manufacturing but also as a highly attractive location for research and development, particularly in the conduct of clinical trials and other services. Indian and foreign companies are continuing with patented drug launches in India and between 2005 and 2010, the Indian patent office has granted 3,488 product patents, as per a KPMG report. However, this also means that Indian companies that achieved their status in the domestic market by breaking product patents, may in the next few years, lose almost $650 million of the local generics market to patent-holders.
To survive in the global market, it becomes imperative that we turn to research with new vigour. We have not contributed prolifically towards the development of new drugs or new medical equipment. Nor have we developed software of medical importance that has gained worldwide acceptance. Prime minister Narendra Modi recently expressed concern over this state of affairs when at the 42nd convocation of All India Institute of Medical Sciences, he said that India is lagging behind in the field of medical research and more work should be done. He exhorted focus on case history,and said that our research ‘can be a big contribution to humankind’.
There is a desperate need to strenghten medical research in the country. Improving infrastructure is first priority alongwith creating an enabling environment and incentives for research.
Training in research methodology can go a long way. At present, no structured training of research methodology is taught in medical colleges. As a result of inadequate training, students are unable to properly and critically analyse and plan research work. Exposure to research in initial stages of their careers can stimulate some medical professionals to undertake research as a major area of involvement. Though every medical postgraduate has to write a thesis/dissertation at present, the quality of their works is often far below standard and hardly worth publishing.
Many physicians and scientists turn into active researchers by virtue of their aptitude or simply due to an overpowering spirit of enquiry. Robert Koch initially a physician went to discover the TB bacillus and Louis Pasteur originally a chemist became the father of vaccinology. In modern times, the concept of bench to bedside, translational science, has brought the integration of laboratory experience to medical practice in a more organised way. But there are disconnects, in India, between the clinician and the scientist, between MD/DM and PhDs. This gulf between basic scientists and clinicians spawns a fair amount of meaningless research. A close physician-scientist interaction is very important to promote translational medical research.
Medical colleges should be ecouraged to foster relations with various research institutes such as ICMR, DST, CSIR and DBT and universities and vice versa. This would help in the collaboration between basic and clinical research and their learning from each other’s expertise and thus enhance opportunities for translational research.
The industry should also devote resources for research particularly within the field of biomedical sciences. Even after increased investment, market leaders such as Ranbaxy and Dr Reddy’s Laboratories spent only 5–10 per cent of their revenues on R&D, lagging behind western pharmaceuticals like Pfizer, whose research budget last year was greater than the combined revenues of the entire Indian pharmaceutical industry.
India has great potential for clinical research with its large number of patients and availability of most disease categories. The right environment and encouragement would help to promote the quality of medical research. With our intellectual strength, it is time for us to be a global player in contributing to the field of medical research.
(The writer is chairman, cardiology department, Max Healthcare Institute, New Delhi, former head, cardiology department AIIMS,
New Delhi, former director and head of cardiology PGIMER, Chandigarh)
Source | Financial Chronicle |
13 October 2015
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