News Article | February 15, 2017
Professor Sujoy K. Guha is undeniably stylish. A short, slender man, he is among the select few who can pull off a pair of sneakers with formal shirts and trousers. At 76, he is deceptively brisk, guiding me around the Indian Institute of Technology (IIT) Kharagpur campus to show off his new projects: an artificial heart modeled on the 13-chamber heart of the cockroach; a road transport system to lower vehicular pollution. Guha is cheerful and poised with a birdlike quaver in his voice, not at all how I expected a man who has waited 37 years for his work to be introduced to the world. In 1979, Guha published a paper in the scientific journal Contraception laying out the idea for his original drug molecule Risug, a non-hormonal, reversible male contraceptive. His idea is simple: All particles carry an electric charge and can be defused by the opposing charge. Sperm are negatively charged and can be defused by the positive ions of the Risug drug polymer. This polymer is inserted with a single injection to the scrotum, which forms an indissoluble film inside the vas deferens—the duct connecting the testes to the penis. The drug formulation for this injection is styrene maleic acid anhydride with dimethyl sulfoxide (SMA+DMSO). A male contraceptive is an unusual thing. Almost the entire range of contraceptive methods available target the female body. The UK's National Health Service website sums up this state of affairs well: out of 16 choices listed for 'methods of contraception', 13 are female. The options for men are condoms (a method whose effect is very limited-term), vasectomy (whose effect is irreversible) and withdrawal. In October of 2016, there was news that the clinical trial of a hormonal male contraceptive, in development for several years, was being stopped on account of side-effects experienced by trial subjects. As of this moment, Risug is possibly the only long-term, reversible male contraceptive in development in the world. (And it's non-hormonal and cheap to boot.) Two years ago, Motherboard wondered why Risug wasn't on the market yet. The average time for a drug to go from idea to market is 10 to 15 years (presumably in the developed world). Now, half of Guha's life later, the word from the Indian Council of Medical Research is that Risug is finally on the cusp of approval. Testing has been completed on 282 subjects across ten hospitals, and the results are nothing short of miraculous—Risug has shown complete effectiveness with zero side effects. A 2011 report by the Ministry of Health and Family Welfare mentioned finding no side effects for the drug in the long-term (a period of nine to ten years), as well as full efficacy. When the 300th volunteer is tested, the Indian Council of Medical Research will formally submit the application for approval to the Central Drugs Standard Control Organization, which is similar to the American FDA. An original drug molecule devised by an Indian individual is a very rare thing. Only two Indians have been credited with such an accomplishment—Dr. U.N. Brahmachari introduced Urea Stibamine to treat Kala Zar, a deadly tropical diseases carried through sand flies; and Dr. Amiyo B. Kar for Centchroman, a nonsteroidal female contraceptive. Guha will be the third. "I have shortlisted two sites for production in Delhi. The knowhow is ready, we just have to scale up from my lab workshop. The sale of my flat is almost finalized," Guha told me. "I am not waiting for a company any longer. I am a scientist, not a marketing man." The professor has been at this juncture before. Fourteen years ago, the then Union Health minister, who oversees public health programs, had announced the imminent availability of Risug in the market, and the news was published in leading national dailies. Just before this, the Ministry of Health and Family Welfare had announced an extension of the clinical trials in support of the drug's imminent production. Then, someone in the Indian Council of Medical Research (ICMR) raised an alarm that Risug led to higher levels of albumin in urine. Guha countered with evidence that albumin levels in men increased across the hot, thirsty months of the Indian summer, when the heat robs bodies of vital nutrients. There was also another problem. In the early 2000s, the Indian government set about tightening the rules for drug approvals among other intellectual property (IP) rights requirements. The timeline granted under the defining Trade-Related Aspects of Intellectual Property Rights (TRIPs) agreement of the World Trade Organisation (WTO), framed in 1995 by the WTO's former avatar known as the General Agreement on Tariffs and Trade, was drawing to a close. The ICMR decided to adopt a set of Good Manufacturing Practices (GMP) and Good Laboratory Practices (GLP) for clinical drug trials. Even if there had been a case for allowing Risug to be tested in the older framework of rules, the drug had been discredited. Everything had to start over. At that time, Guha approached then Indian President Abdul Kalam for help. Kalam is a famous orator, known as a man of science himself, having spent his life working for the Indian national program on nuclear weapons. "He told me, 'Sujoy, you know this is not a scientific block. You have to solve this in other ways'," Guha said. Rejection. Anger. Mellowing. Acceptance. "Sir used to say that every invention takes its maker through four stages," said Dr. Sohini Roy, a biologist who did her PhD under Guha and is now a postdoctoral fellow at UCLA. "He prepared us well for life." When Guha and his co-authors published the first paper on Risug in the international research journal Contraception, he was just 40 years old. He was a professor with both the Indian Institute of Technology Delhi and the All India Institute of Medical Sciences (AIIMS), two of the most renowned institutions in the country, and already had the reputation of a maverick. But he was not a medical doctor, and the ICMR would not consider a drug molecule devised by a non-medically trained individual for clinical trials. At the age of 41, Guha took the medical entrance examination for Delhi University and passed. He completed his medical degree studies while continuing to teach electrical engineering at IIT and biomedical engineering at All India Institute of Medical Sciences (AIIMS). When the clinical testing process began, trials on rats and rabbits (smaller animals) and monkeys (larger animals) moved fairly fast and proved successful. Phase-one of the human clinical trials on 17 volunteers was completed in 1993. It went perfectly. Then, someone photocopied sections from a book called Hazardous Chemicals: Desk Reference and sent them to the national research council. The sections in question listed styrene and maleic anhydride, both part of Risug's formulation, as carcinogens. Guha had to counter again: he argued that substances can be individually toxic in nature but harmless as compounds. He gave the example of pure chlorine, which can melt human flesh on its own, but combined with sodium, it becomes sodium chloride, the basic salt that we consume in our diets. When trials did not resume by 1996, the professor petitioned the Supreme Court. The court dismissed Guha's petition in five minutes, saying they were not the competent authority to rule on it. But it seemed to have sent a message to the government. Phase-two resumed. The antagonist in Risug's story is not the Indian government, according to Guha, but the international pharmaceutical lobby. "The government has, in fact, put in a lot of time and money for the clinical trials," he said. "In the first place, there would be no trials without them." Many of the questions raised about Risug and the resultant delays have been instigated by the National Institutes of Health (NIH) in the US, he contends. For several years, the agency wanted to promote a drug for men that involved regular ingestion like the female pill, Guha said. The first medical practitioner to administer Risug for clinical trials, Dr Gulshanjit Singh, told me a similar thing some years ago. The NIH, he said, was batting for a hormone-based, repeat-use drug developed by a US-based firm. He remembered meetings where a section of the ICMR argued strongly in favour of this American drug, and pointed out problems with Risug. Singh served as the head of the department of surgery in Safdarjung Hospital and Deen Dayal Upadhyay hospital, two prestigious publicly-funded hospitals in New Delhi. Recent developments seem to support this claim. The drug whose trials were stopped in October 2016 was a hormone-based solution, relying on regular ingestion to control the production of hormones. Regular use implies long-term sales, a steady guarantee of profit. Risug, on the other hand, requires a maximum of two doses--one injection to put the polymer film in place, and another to flush it out of the vas deferens. "In fact, even in the World Health Organization (WHO), there are people who don't want the drug [Risug] to come through," A.R. Nanda, the Union health secretary from 1999-2002, told me. Then, in 2002 came the albumin charge that halted Risug trials, and subsequently the ICMR decided to put Risug through the new framework for clinical drug trials. The clock turned back to the start. Soon after 2002, the professor came away to IIT Kharagpur. He had enrolled in the seventh batch of IIT Kharagpur in 1957. It was the first IIT to be established in India--the first child of prime minister Jawaharlal Nehru's technology-centric national project--and when the professor attended, it was still suffused with a romantic sense of national service. Here in Kharagpur, he established the Risug Center With a new batch of students and researchers. This includes a laboratory, where they produce the drug used in the clinical trials of Risug. When the approval comes through, Guha's team has the knowhow to scale up from the few hundred units they currently produce, to several thousands for market production. There's also another personal history: his maternal uncle was imprisoned for eight years (in three separate terms) by the British colonial administration at the infamous Hijli detention camp here. But he survived it. "From my mother's side of the family, I get my obstinacy. And my father, I saw him kill himself looking after his patients in Patna [the capital of Bihar]. I learned how to keep a job from him," he said. Guha is both a good storyteller, frank without being self-deprecating, realistic and philosophical. He rarely answers a question when you ask it; he gives every question thought and more often than not, he decides it's not worth his time to answer. It takes a certain kind of temper to be a scientist in the Third World. To not be worn out by the waiting, and form-filling, and inevitable jealousies--among peers, bureaucrats, and scientists in other countries. Guha knows this. He makes sure to sleep. He jogs every night because it makes him feel like himself. He tucks his shirt in and combs his silver hair carefully. When I asked Guha if he felt more anxious now than he had in 2002, he walked ahead of me without answering. I thought he wasn't going to answer, but he turned around some seconds later. "One hopes that I have learnt something. I am no longer an angry man." A longer profile of Prof Guha and Risug was published in The Wire .
News Article | November 15, 2016
A controversial, Frankenstein-esque experiment that would attempt to revive brain-dead accident victims has been deregistered from India’s clinical trial registry. The Indian Council of Medical Research (ICMR) cited multiple reasons for halting the “ReAnima” trial, including failure to obtain permission to proceed from the Drug Controller General of India, which is a necessary step in all clinical trials conducted in the country. Laboratory Equipment reported on the “ReAnima” experimental trial in May 2016, after it received institutional review board approval from the IRB at the Anupam Hospital in Rudrapur, Uttarakhand, India. The trial, which was supposed to run until April 2017, was formed from a partnership with two biotech companies - Revita Life Sciences of India, which specializes in stem cell therapy, and Bioquark, a Philadelphia-based company that would supply the trial with specialized chemicals to regenerate brain cells. According to a press release published by the two companies, the leaders of the trial were interested in learning more about how some species in nature—like amphibians, planarians and certain fish—can regenerate brain matter even after traumatic injury. The underlying mechanics of this ability could theoretically be applied in human models. “Through our study, we will gain unique insights into the state of human brain death, which will have important connections to future therapeutic development for other severe disorders of consciousness, such as coma, and the vegetative and minimally conscious states, as well as a range of degenerative CNS conditions, including Alzheimer’s and Parkinson’s disease,” Sergei Paylian, the founder and chief science officer of Bioquark, said after receiving initial approval in May. The ultimate goal of the exploratory work was to bring brain-dead patients back to a “minimally conscious state.” The team of scientists planned to do this by administering BQ-A peptide extracts and mesenchymal stem cells directly into the brain shortly after a patient had been declared brain-dead. They would also use transcranial laser therapy and median nerve stimulators as an “intervention” to essentially jump-start activity in the neural cells. The team planned to test this procedure on 20 patients in India, but Ira Pastor, CEO of Bioquark, admitted to Science that the team was having trouble getting permission from family members to enroll their loved ones in the trial. Additionally, news of the ReAnima trial sparked controversy among other researchers when it was first announced in May. There have been rare reports of brain-dead patients returning to full function, but evidence is still too scarce to support the theory that doctors could reverse such significant brain damage with repeated success. The question of ethics also came up as the mix of injections the team intended to administer to human patients hadn’t been tested in animal models. Partially reviving brain dead patients may also traumatize family members, researchers argued. Pastor told Science that despite the setback, the team intends to move forward, even if they have to move the trial outside of India. “Many road blocks, no doubt, will pop up. But the project will go on,” Pastor said.
News Article | November 16, 2016
A controversial experiment to revive brain-dead accident victims has been scrapped. The Indian Council of Medical Research’s (ICMR) National Institute of Medical Statistics officially removed the “ReAnima” trial from India’s clinical trial registry on Nov. 11. The experiment began in May when Himanshu Bansal, an orthopedic surgeon at Anupam Hospital in the north Indian state of Uttarakhand, announced plans to give approximately 20 brain-dead people a mix of interventions including injections of mesenchymal stem cells, peptides, transcranial laser stimulation and median nerve stimulation. Transcranial laser stimulation is a process that involves shinning pulses of near-infrared light in the brain, while median nerve stimulation is the electrical stimulation of a major nerve that runs from the neck to the arm. Both techniques have been proven to improve cognition in patients with traumatic brain injury. The ICMR identified several regulatory lapses in the trial that led to the decision, including a failure to seek permission to proceed from the Drug Controller General of India, a requirement for all clinical trials in India. Bansal previously described his aim as bringing brain-dead individuals back to a minimally conscious state where patients show flickers of consciousness like moving their eyes to track objects. While there is little evidence to show that brain-dead people can recover with function, Bansal has maintained that there is a significant number of cases of people who have recovered full consciousness from a minimally conscious state. However, other researchers have doubted the project, claiming that situations where brain-dead individuals on life support who return to a fully functional state is hard to interpret and often lack evidence of brain death such as the apnea test, a measure of whether the person’s brain stem is making an effort to breathe. Other concerns raised by scientists and physicians include whether the trial is ethically justified and that the mix of interventions has not been tested in animal models. In a press statement, Bansal defended the proposal, saying there is no good animal models for human brain death.
News Article | November 14, 2016
BENGALURU, INDIA—The Indian Council of Medical Research (ICMR) has derailed a controversial experiment that would seek to revive brain-dead accident victims. On 11 November, ICMR’s National Institute of Medical Statistics removed the “ReAnima” trial from India’s clinical trial registry. In May, Himanshu Bansal, an orthopedic surgeon at Anupam Hospital in the north Indian state of Uttarakhand, announced plans to give around 20 brain-dead people a mix of interventions including injections of mesenchymal stem cells and peptides, and transcranial laser stimulation and median nerve stimulation. Transcranial laser stimulation involves shining pulses of near-infrared light into the brain; median nerve stimulation is the electrical stimulation of a major nerve that runs from the neck to the arm. Both techniques have been shown to improve cognition in patients with traumatic brain injury. Bioquark, a biotech firm based in Philadelphia, Pennsylvania, had agreed to supply the trial with peptides that are said to help regenerate brain cells. In interviews with Indian media in the spring, Bansal described his aim as bringing brain-dead individuals back to a “minimally conscious state” in which patients show flickers of consciousness, such as moving their eyes to track objects. Although there is scant evidence that brain-dead people can recover such function, Bansal says the medical literature describes a significant number of cases of people who have recovered full consciousness from a minimally conscious state. Other researchers point out that it is improbable that the ReAnima trial—which hasn’t yet begun—would achieve its goals. “While there have been numerous demonstrations in recent years that the human brain and nervous system may not be as fixed and irreparable as is typically assumed, the idea that brain death could be easily reversed seems very far-fetched,” Dean Burnett, a neuroscientist at the United Kingdom’s Cardiff University, told . Medical journals have on occasion carried reports of brain-dead individuals on life support returning to a fully functional state, but researchers have argued that such cases are hard to interpret and often lack evidence of brain death such as the apnea test, a measure of whether the person’s brain stem is making an effort to breathe. Scientists and physicians are also raising concerns about whether the ReAnima trial is ethically justified. One concern is that the mix of interventions has not been tested in animal models. On their own, the treatments the ReAnima trial would use have shown promise in people with traumatic brain injury, says Amar Jesani, editor of the in Mumbai. “But once brain stem death has taken place, and there is no cognition or consciousness, one cannot rely on a few disconnected studies. Why couldn’t they combine these interventions and do proper animal studies?” And even if the experiment were to succeed, he asserts, bringing a brain-dead person back to a minimally conscious state would traumatize family members. In a press statement, Bansal argued that there are no good animal models for human brain death. Asked in a June interview for what he planned to do if patients were brought back to a minimally conscious state but did not regain further function, Bansal responded that his team “had not planned for it” initially, but that he had since purchased an insurance policy to cover the costs of full-time care of such patients. Still, the ReAnima team has struggled to convince family members to allow brain-dead accident victims to be enrolled in the trial, says Ira Pastor, chief executive officer of Bioquark. ICMR identified several regulatory lapses in the trial, including a failure to seek permission to proceed from the Drug Controller General of India, a requirement for all clinical trials in India. Now that ICMR has deregistered ReAnima, the Drug Controller General of India G. N. Singh must stop the trial immediately, says ICMR Deputy Director General Geeta Jotwani in New Delhi. Bansal told that “ICMR has nothing to do with the trial,” and says the matter rests with the drug controller. Singh’s office did not respond to questions from . Bioquark’s Pastor says that the setback ultimately won’t stop the project, and if necessary the team would pursue the trial outside India. “We are in no major rush, in that it represents a ‘Google Moonshot’–style project,” he says. “Many road blocks, no doubt, will pop up. But the project will go on.”
Singhal S.,Lok Nayak Hospital |
Kohaar I.,Institute of Cytology and Preventive Oncology ICPO |
Bharadwaj M.,Institute of Cytology and Preventive Oncology ICPO |
Shukla D.K.,ICMR |
And 2 more authors.
Digestive Diseases and Sciences | Year: 2010
The key elements that determine the host response to either the self-limited or a severe fulminant form of liver disease are unclear. We have investigated the potential association of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-alpha (TNFα) in their susceptibility to acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting specific viral etiology. A total of 124 individuals including 64 cases comprising 27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at -238 (G/A), -308 (G/A), -857 (C/T), and -863 (C/A) of TNFα were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing. Serum levels of TNFα were determined at admission and death or recovery. Association between the TNFα genotype and susceptibility to FHF was not evident; however, carrier genotypes in relation to the -308 (GA/AA) and -857 (CT/TT) loci were found to be significantly (P ≤ 0.05) associated with susceptibility to AVH in relation to controls. The mean TNFα serum levels at admission were significantly higher (P < 0.001) in FHF than AVH patients, but no marked difference was observed between FHF-E (expired; n = 17) and FHF-S (survivors; n = 10), though the former were comparatively higher. This study suggests that SNPs at -308 and -857 of the TNFα promoter may represent an increased risk for the development of AVH but not for FHF in the Indian population. © 2009 Springer Science+Business Media, LLC.
Agrawal S.,P.A. College |
Khandelwal K.,P.A. College |
Bumb R.A.,P.A. College |
Oghumu S.,Ohio State University |
And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2014
Cutaneous leishmaniasis (CL) is endemic in the Bikaner region situated in the Thar Desert of Rajasthan, India. This study describes clinicoepidemiological data of pediatric CL in pre-school children (0-5 years of age) from this region during 2001-2012. In total, 151 patients with 217 lesions were reported during the study period. The mean age of the study group was 3.29 ± 1.43 years (0.25-5 years), with many (41.7%) cases being in the age group of 2-4 years. Face was the most common site involved, and morphologically, the lesions were either plaque type or papulonodular. Smear for parasitologic examination was positive in 84 (70%) of 120 cases, and histopathologic examination confirmed CL in 10 (55.55%) of 18 cases. Parasite species identification conducted for 13 randomly selected patients by polymerase chain reaction identified Leishmania tropica as the causative species. Intralesional sodium stibogluconate was the most commonly used treatment and found to be well-tolerated. Other therapies that were effective included oral rifampicin, oral dapsone, radiofrequency heat therapy (RFHT), and combinations of the three therapies. Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.
Desikan P.,Bhopal Memorial Hospital |
Chakrabarti A.,Jawaharlal Institute of Postgraduate Medical Education & Research |
Indian Journal of Medical Microbiology | Year: 2011
Ethical issues facing microbiologists could be considered in two parts. The first relates to the way the ethical issues during their laboratory work. The second pertains to ethical issues on the data/reports they generate for the patients or in research. In both segments, there is pressure to perform, which is exerted by both, the community, as well as peers. It has therefore become increasingly necessary to recognize the facts that unethical actions might be a frequent reality. Since some of these activities generate serious ethical concerns, both in practice and research, it is necessary for microbiologists to be aware and equipped to meet these issues in a prepared and measured way.. In an attempt to highlight this requirement, this article outlines the important ethical issues and guidelines relevant to the field of Microbiology.
Singh S.,ICMR |
Paul K.,Indian Institute of Technology Delhi |
Yadav G.,Indian Institute of Technology Delhi |
Prasad S.,Indian Institute of Technology Delhi
HEALTHINF 2016 - 9th International Conference on Health Informatics, Proceedings; Part of 9th International Joint Conference on Biomedical Engineering Systems and Technologies, BIOSTEC 2016 | Year: 2016
The simplified Partograph is a concise charting mechanism used by skilled birth attendants for recording and communicating the important parameters and developments during the labour process. Compliance and correct plotting of partographs may be significantly improved with the use of technology. This paper reports the development of an Android-based smart phone/tablet application to plot the partograph. To date such a complete application is not available. We envisage that over a period of time, systematic plotting of partographs will encourage providers to use it as a decision-making tool and thereby reduce morbidity and mortality both of mother and foetus/newborn arising out of complications during labour and its sequelae. Copyright © 2016 by SCITEPRESS - Science and Technology Publications, Lda. All rights reserved.
Raina S.K.,P.A. College |
Chander V.,P.A. College |
Raina S.,P.A. College |
Journal of Neurosciences in Rural Practice | Year: 2016
Background: Mini-mental state examination (MMSE) scale measures cognition using specific elements that can be isolated, defined, and subsequently measured. This study was conducted with the aim to analyze the factorial structure of MMSE in a largely, illiterate, elderly population in India and to reduce the number of variables to a few meaningful and interpretable combinations. Methodology: Principal component analysis (PCA) was performed post-hoc on the data generated by a research project conducted to estimate the prevalence of dementia in four geographically defined habitations in Himachal Pradesh state of India. Results: Questions on orientation and registration account for high percentage of cumulative variance in comparison to other questions. Discussion: The PCA conducted on the data derived from a largely, illiterate population reveals that the most important components to consider for the estimation of cognitive impairment in illiterate Indian population are temporal orientation, spatial orientation, and immediate memory.
Raizada A.,Mahatma Gandhi Medical College |
Johri V.,Ravindranath Tagore Medical College |
Ramnath T.,ICMR |
Chowdhary D.S.,Mahatma Gandhi Medical College |
Garg R.P.,Mahatma Gandhi Medical College
Journal of Clinical and Diagnostic Research | Year: 2013
Introduction: Dermatoglyphics is a collective term for all the integumentary features (skin patterning of the fingers, toes, palms and soles) and it applies to the division of the anatomy which embraces their study. Aims and Objectives: The purpose of this study was to examine the predominant finger tip patterns in the patients of carcinoma breast. An attempt is also being made to devise a score to assess the risk variables. Materials and Methods: The fingerprints of 100 carcinoma breast patients were obtained and they were compared with those of 100 females who were not suffering from any malignancy till date. The different quantitative parameters of each hand of both the cancer patients and the controls were studied. The parameters which were included were the fingertip ridge pattern, the ridge count in the individual fingers, the To- tal Finger Ridge Count (TFRC) and the Absolute Finger Ridge Count (AFRC). Results: There was a significant increase in the arch pattern and a decrease in the radial loops in the right thumb (p<0.001), the left thumb (p<0.001), the left index finger (p<0.001) and the left middle finger (p<0.001). A comparison of all the five fingers of both the left and right hands of the cancer patients with the controls showed an arch pattern (p<0.001) with the highest frequency. The lower values of the TFRC (below 50) were associated with carcinoma breast. The lower values of the AFRC (below 100) were associated with the cancer patients. Conclusion: This study was able to establish a specific finger tip predominance in the Carcinoma breast patients.