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Chennai: The Haven of Medical Research

Chennai has become the hotbed for breakthrough medical research work, thus attracting international collaborations, informs Nayantara Som.

Academicians in Hyderabad and Bangalore have competition now. There is another promising contestant in the race. Hitherto, Chennai was mainly associated with medical tourism, mushrooming hospitals and regular influx of patients. This is all passé. Now, the city seems to have gone through a metamorphosis. Today, walk into any hospital and, it is a common feature to see a separate research institute or a medical college attached, where intensive research work is deliberated upon and published.

"In diabetes, out of all Indian publications, around 40-50 per cent comes from Chennai" - Dr V Mohan Chairman Dr Mohan's Diabetes Specialities Centre

Stem cell research, tissue engineering, molecular biology, nanotechnology, clinical and epidemiological studies, gene therapy, research in diabetes, you name it and Chennai has it all. In diabetes alone, experts assert there is no competitor. Dr V Mohan, Chairman, Dr Mohan's Diabetes Specialities Centre and President and Director of Madras Diabetes Research Foundation, Chennai, says, "Chennai is definitely on the world map of medical research. In diabetes alone, if you browse through all the Indian publications, around 40-50 per cent comes from Chennai alone!" Prestigious institutes in the city like the Tuberculosis Research Centre, the Cancer Institute and the Madras Diabetes Research Foundation have come up with pioneering studies, making Chennai the locus of all research studies. Dr Sanjay Cherian, Managing Director, Frontier Lifeline, Chennai, says, "Chennai has a huge pool of experts and at the same time there is a large number of medical colleges growing rapidly."

Collaborations with prestigious institutes abroad and in the country is a continuous process. Dr Samuel Abraham, Director, Nichi Centre for Regenerative Medicine (NCRM), Chennai, elaborates, "In Chennai, there are 14 or more institutes working on basic research and clinical applications of stem cell, which is the largest in any metro in the country, not only in number but also in diverse areas of the speciality."

Tissue Engineering

"When an initiative is taken from clinical side the results are faster and better. This is where Chennai wins" - Dr Samuel Abraham Director, NCRM, Chennai

Tissue engineering is the next big thing in medicine. Currently, it is research in tissue engineering and biological cardiovascular implants that dominates the scenario in Chennai. Research in this field has been an ongoing process for almost three-and-half years at Frontier Lifeline and this has caught the attention of experts in Europe and Asia. Tissue engineering is a process where animal tissues are extracted, studied, processed, decellularised and then used to replace or improve certain biological functions in humans, especially in case of burns.

A state-of-the-art tissue culture laboratory, the Madras Institute of Research, is being set up at the MIOT Hospitals. Dr Soma Guhathakurta, Consultant, Cardiothoracic Surgeon, Director and Research Coordinator, Frontier Lifeline, says, "We were the first to commence research on tissue engineered products in South-East Asia."

"The stem cells are separated and grown in Israel and used in Bangkok" - Dr KM Cherian Chairman, Frontier Lifeline Chennai

In fact for tissue engineering alone, Frontier Lifeline also houses an in-house R&D unit, Frontier Tissueline, at TICEL Bio Park at Taramani, Chennai. The unit is dedicated to undertake advanced research in biological cardiovascular implants. "Research and applications in stem cell, the making of viable scaffolds of autografts and umbilical cord blood storage also constitute some of the core activities of this unit," says Dr S Cherian. Bio-Informatics and computational biology are recent additions to the activities undertaken here. "Small diameter vascular grafts and amniotic membrane processing is going on in our lab. Since inception, of the 15 research papers published, four papers are on Tissue Engineered Products alone. "We have had experts from Israel, France and the Middle East consulting us," says Dr Guhathakurta. The research is funded by the Department of Science and Technology and Department of Biotechnology which suggested the entire idea of tissue engineering. Intensive ongoing research is in process in the field of bovine pericardial patches (as cardiovascular patch materials), bovine jugular veins and porcine pulmonary artery conduit (for children aged one month to 13 years). Dr KM Cherian, Chairman, Frontier Lifeline, says, "At Frontier Lifeline, for bovine jugular veins, we use the vein of the buffalo's neck. This vein can withstand tremendous pressure. We use it mainly in children suffering from congenital cardiac diseases. Similarly for porcine pulmonary artery conduit, we take tissues from pigs." The Hospital has experimented on 150 patients for bovine pericardial patches, 142 for bovine jugular veins, and 31 for porcine pulmonary artery conduit. Other ongoing projects include tissue engineering of homologous natural biomaterial for clinical use; tissue engineering of porcine ureters for cardiovascular use, antimicrobial treatment of xenografts for clinical use; custom-made testing devices for developed xenografts for clinical use; and standardisation and optimisation of effective methods of decellularisation of processed porcine pulmonary artery xenografts.

"For tissue engineered products, Frontier Lifeline's experiments have reached the perfection of the native tissue. No other institute has reached that perfection," adds Dr Guhathakurta. Developing biological implants and devices to perfection for human use has already been initiated by making biocompatible xenografts and patches. Frontier Tissueline also includes in its functions biological and development of biocompatible synthetic valved conduits as another achievement of this unit.

The use of indigenous products has shown monetary benefits. Prices of these tissue engineered products at Frontier Lifeline could cost from Rs 30,000 to Rs 40,000. Usually imported conduits made abroad comes from Rs 2,75,000 onwards.

Diabetes

When it comes to diabetes research, there is none to beat Chennai. A testimony to this: Two of the largest diabetes research centres in this country, the Madras Diabetes Research Foundation (MDRF) and the Diabetes Research Centre Foundation (DRC) are both located in the city and between them produce almost half of all research on diabetes done in India. The MDRF, recognised as an ICMR Advanced Centre for Research, has conducted several path breaking research studies. Large scale studies have been conducted in aspects of epidemiology, nutrition, and diabetes retinopathy and genomic aspects.

The MDRF also specialises in myriad aspects of diabetes like diabetic complications, clinical trials, epidemiology, genomics, vascular biology and nutrition research. Founder Dr V Mohan's wife, Dr M Rema, specialises in diabetic retinopathy research. In fact, in diabetic retinopathy, the centre has come up with an innovation. Informs Dr Mohan, "Retinal cells are grown here. Usually in eye donations only the front portion of the eye is used and the rest is dumped. My wife uses those parts which would otherwise be dumped for research on the cells of retina and find out the effects of diabetes on the eye." The centre is also involved in two major epidemiological studies - the Chennai Urban Rural Population Study (CUPS) and the Chennai Urban Rural Epidemiology Studies (CURES). In CUPS, the, urban population is divided into people living in residential colonies and people living in the slums. Comparisons are made on prevalence of diabetes, hypertension and the metabolic syndrome. Likewise, in CURES, Chennai is divided into corporation zones and people are selected for studies. "We have published around 438 papers on diabetes including 50 last year alone which is a record of sorts," informs Dr Mohan.

There is also research happening in genomics. "We study the genetic aspect of diabetes. Around four to five experts in our centre are involved in genomics alone," says Dr Mohan. Professor A Ramachandran, Managing Director, MV Hospital for Diabetes and Diabetes Research Centre Foundation, Chennai, says, "We proved that India is the hub for diabetes and will continue to be so. This is because, Indians have a low threshold for conventional risk factors. However, it was also found that diabetes is partly genetic and partly environment. There has been a 20-fold increase in diabetes among the urban population in India, which cannot be attributed to genes alone. This is due to the lifestyle habits of the people." Another randomised control trials under Professor Ramachandran had conducted an interesting study beginning 2001 and published in 2006, which was a part of the primary prevention of diabetes, whereby 530 people with high risk diabetes, were divided into four groups. In group one, there was no intervention in the lifestyle of the people, in group two there were moderate modifications of lifestyle, in group three, medicines were given and in group four, medicines along with lifestyle modifications. "These studies were conducted in Finland and the USA, but to conduct the same in India, researchers found it difficult because patients here do not get into the habit of exercise and lifestyle modifications. We took it up as a challenge," says Prof Ramachandran. After three-and-a-half years, it was found that the incidence of diabetes in patients had dropped in these patients by 30 per cent! "This is a clear indication that diabetes if caught at an early stage can be controlled and prevented," informs Prof Ramachandran.

Chennai boasts of a pool of experienced medical experts, making it a conducive ground for research

Now a post-prevention analysis based on the same study is being conducted. The economics of diabetes healthcare is another area of study where the cost of illness of a diabetic patient is studied. Another interesting study proved that ‘Yogasanas’ might be used as an adjunct with diet and drugs in the management of Type 2 diabetes. Dr Vijay Viswanathan, Managing Director, MV Hospital for Diabetes and Diabetes Research Centre Foundation, Chennai, who was a part of the study published recently, says, "The study was conducted to prove the concept that newly detected Type 2 diabetic subjects with near normal HbA1c could be treated with alternative methods such as yogasana." There are also a couple of large scale collaborations for the centre. The prime collaboration is the designation bestowed by the World Health Organisation (WHO), Geneva as a WHO collaborating Centre for Research, Education and Training in Diabetes in India. Dr Viswanathan, says, "Through this collaboration, the WHO Collaborating Centre is directly participating in all WHO-sponsored projects and programmes related to diabetes mellitus. The list of collaborations for research goes on. Prof Ramachandran add, "We have collaborated with London School of Hygiene, University of Helsinki, Royal College Hospital in Britain, Australia and University of Cambridge, UK. These collaborations help us to publish papers together and work together." Research work with the European Union is also in progress.

Similarly,Sankara Nethralaya is also involved in large epidemiological studies in glaucoma and diabetic retinopathy. They have completed prevalence studies and now have started incidence studies. Grants from private trusts such as Willingdon Trust and R D Tata Trust have made it possible to conduct such large epidemiological studies which have an important bearing on the planning from the Health Sector. Dr SS Badrinath, President and Chairman, Medical Research Foundation, Sankara Nethralaya, says, "We are doing a lot in diabetic retinopathy, genetic studies in diabetic retinopathy and basic science work. We have 100 projects ongoing."

Ophthalmology

The big one that is coming in the way for the city, is Sankara Nethralaya's National Institute for Research in Visual Sciences and Ophthalmology (NIRVO). Dr Lingam Gopal, Chairman-Elect, Sankara Nethralaya, says, "We should be able to inaugurate it by March next year."

Agrees Dr Badrinath, "This will be a meeting of many scientific minds." An MoU has already been signed with the Department of Biotechnology and the National Institute of Health, Bethesda USA, which will help in the exchange of scientific research, and material for collaborative efforts.

The latest on the cards is research in nanotechnology. Nanotechnology, pundits predict, is out to change the face of healthcare. Says Dr Gopal, "We are trying to use nanotechnology to facilitate the penetration of molecules inside a target cell. Retinoblastoma is a cancer of childhood and can potentially lead to threat to eye as well as life. The disease is fairly common and on an average we see nearly three-five cases per week. The eye may have to be removed in advanced cases while others may sometimes respond to chemo therapy. Using nanotechnology, we are currently researching into the possibility of a drug targeting the tumor cells selectively, thereby reducing the toxicity to other tissues and improving the efficacy in destroying the tumor itself," adds Dr Gopal. At present, an expert from Sankara Nethralaya has been granted a fellowship by ICMR to pursue research in the field of nanotechnology with US-based scientists.

With this novel idea, Sankara Nethralaya is planning to collaborate with two- to three centres, which makes nano particles and antigens. "This includes collaboration with the Government of India Centre, Bhubaneswar, that will make the nano particles for us, and for antibodies we are collaborating with IIT," informs Dr Gopal. The study has been approved by the DBT and is scheduled to start soon.

An initiative by the department of science and technology of the Government of India brought together scientists who developed the DNA chip. This is the brain child of Dr H N Madhavan, Director of Research. “The chip helps to identify selected organisms at one go. Take a blood sample of a person suffering from an infective disease, put one drop on the chip and process it. This chip will be able to identify up to 14 organisms in one shot,” informs Dr Gopal. The chip is undergoing trials now and will be sold in the open market soon. DST has also identified a company to market this. This DNA chip will also be tested at Sankara Nethralaya.

Stem Cell Research

Stem cell research is another prime area of focus for Chennai. "Research on cardiovascular diseases is ongoing by our genetic engineering lab," says Dr Guhathakuta. In basic research, a project on bone marrow transplant is underway and is partly funded by the ICMR. The Phase I trial with bone marrow derived stem cells with conditioning media is currently underway at the research facility at TICEL Bio Park. In Phase II, progenitor cells harvested from blood and entirely autologous are the best cells available and ready for clinical use. A technique is adopted whereby an injection (GcSF) is given for three days and subsequently the mononuclear stem cells are isolated by aphaeresis technique. These cells are injected during surgery into the myocardium in the cardiac catheterisation laboratory. This was performed in collaboration with Sri Venkateswara Institute of Medical Sciences, Tirupati. "This procedure has been performed in eight patients and another 20 patients are waiting," says Dr S Cherian.

"The stem cells are separated and grown in Israel and used in Bangkok. There are more than 100 people waiting for this treatment. The cost in Bangkok for each patient is around $34,000 (including hospital stay). In India, we could do it for $5,000,"says Dr KM Cherian.

Another project to look forward to is the Bio-Sciences Park, within the proposed Medicity, spearheaded by Frontier Lifeline, which will harbour a unit specially for R&D. Plans are on the anvil in which expert training, in the field of tissue engineering, for the whole of South East Asia will commence.

Again Sankara Nethralaya is involved in stem cell research like corneal limbal cell research. If limbal stem cells are affected due to conditions such as acid or alkali burns, Steven Johnson syndrome etc, corneal grafting usually fails. By transplanting limbal cells the success of grafting can be significantly improved. The practice has been to grow limbal stem cells on amniotic membranes. Dr H N Madhavan, Director of research at Sankara Nethralaya was able to grow these limbal cells on a polymer (mebiol gel) in association with Dr Abraham from Japan. We have been involved in this study since 2002 and after the animal experimentation which was completed, we are awaiting ICMR approval for the human trials.

The NCRM, Chennai (a Japanese collaboration) is collaborating with Sankara Netharalaya for this project. The unique advantage here is there no usage of animal tissue or human tissue and so no possibility of rejection. Cells are to be taken from patients' own normal eye or normal portion of the affected eye. One scientist is undergoing training for a year from an expert specialising in neuro stem cells. There is research ongoing in neuro stem cells. Attempts are being made to convert a particular stem cell into a retinal nerve cell. "That, of course, is going to take decades before it can be introduced," adds Dr Gopal.

Sankara Netharalaya has put in place multiple partnerships for research. Broad based MoUs have been inked with LV Prasad Eye Institute in Hyderabad and Aravind Eye Clinic, Madurai. "We are at a stage where we can bring together all our resources for better work," says Dr Gopal. Other than broad-based agreements, there are individual-based agreements. The institute conducts drug trials for companies, with scientists from the US, New Zealand and Japan.

In technology,a recent acquisition is the Affymetrix machine, a state-of-art technology that does genetic analysis. Millions of genes can be looked and tested in one shot. An analysis that would take one year to identify the gene, will now take few days.

NCRM is also working on Corneal Endothelial Precursor Cells in collaboration with Tokyo University School of Medicine, who gave the technology and specimens and the harvesting was accomplished by Joseph Eye Hospital, Trichy. This project is at the lab level and aims at treating bullous keratopathy, a disease that affects a lakh patients, each year. It affects the inner layer of the cornea, for which total corneal transplant is an option now. "By our technology, we have to take a few hundred cells from cadaver corneal endothelium (inner layer) and expand it to be put in the respective portion for cure, by doing which, the inner layer of cells of cornea of one cadaver eye can help recover the vision of a minimum of 40-60 people."

Hurdles Faced

"Bangalore and Hyderabad boast of some of the best institutes in the country and the government allocates large amounts of money for infrastructure and development of these institutes. Chennai does not have such institutes and hence the opportunity for multisectoral research are less than Bangalore or Hyderabad," says Dr Mohan who is also the President of the Madras Science Foundation. He, however, feels that there is enough funds available from various government agencies like ICMR, DBT, DST and CSIR.

"We need more money for medical research in India. It is currently difficult to get funds for medical research in our country. Similar to the situation in US and UK more organisations should donate money for medical research," says Dr Viswanathan.

The Road Ahead

There are other experts in the city who beg to differ and are firm on their stand that Chennai rules the roost. Says Dr Abraham, "Though several prominent central government research institutes are present in Hyderabad and Bangalore (CCMB, IISc, NIMHANS), the gap between clinical faculty and basic sciences is too large in India. When an initiative is taken from clinical side the results are faster and better. This is where Chennai wins."

The future is bright for Chennaites. "There is a lot in store for stem cell research. There is going to be stem cell research in plastic surgery, in orthopaedics and for cardio-vascular diseases," says Dr S Cherian. In cases like diabetic ulcers and where a body part has to be amputated, stem cell therapy is a solution to free patients from this nightmare. Moreover in diabetes, large scale studies are on like the primary prevention programmes and awareness programmes. Experts also predict the coming together of biotechnological and pharmaceutical companies with the medical profession.

"A few partnerships are happening. The city is seeing and will see clinical trials, genetics, advances in insulin and vaccines and above all the why's and how's of diabetes," says Dr Viswanathan. The Tuberculosis Research Centre is patenting a drug for HIV/AIDS. Construction of a new research facility of MDRF at SIRUSERI in the outskirts of Chennai is now nearing completion and is slated for inauguration in 2-3 months. This project will take the research at MDRF to the next level of basic research involving proteomics, tissue culture, stem cells and development of gene chips for accurate genomic classification of different subtypes of diabetes. As far as funding is concerned, institutes are concerned about solutions rather than whining about paucity. Collaborations both within and outside the country is a huge source for bringing in money. We sometime donate our own personal funds for conducting research projects." says Dr. Viswanathan. "Sometimes hospital donate their own profits for the research projects,” adds Dr Viswanathan.

An optimistic approach is shared by a majority of experts from the city and perhaps it will be this approach which can keep Chennai ahead in the rat race.

nayantara.som@expressindia.com