Sunset Yellow induced biochemical and histopathological alterations in rat brain sub-regions.

Sunset Yellow, a synthetic orange azo food dye was examined in this study for its impact on the Wistar rat brain sub-regions. The dye was administered orally to weanling rats at the Acceptable Daily Intake level (4 mg/kg/bw) for 40 days, and brain sub-regions viz., frontal cortex, cerebellum and hippocampus were examined for biochemical and histopathological changes. The results showed a significant decrease in tissue protein levels, superoxide dismutase, and catalase activity, as well as a significant increase in lipid peroxide levels in all brain sub-regions. Glutathione-S-transferase and Glutathione Reductase activities decreased, while Glutathione peroxidase activity increased. The biogenic amine levels and Acetylcholinesterase activity were also altered, with the frontal cortex and hippocampus being the most affected. Additionally, the dye caused histopathological damage in all brain sub-regions examined. This study indicates that the ADI level of Sunset Yellow may adversely affect brain tissue by causing oxidative damage.

Tartrazine induced neurobiochemical alterations in rat brain sub-regions.

Tartrazine is a synthetic lemon yellow azo dye primarily used as a food coloring. The present study aimed to screen the neurobiochemical effects of Tartrazine in Wistar rats after administering the Acceptable Daily Intake (ADI) level. Tartrazine (7.5 mg/kg b.w.) was administered to 21 day old weanling rats through oral gavage once daily for 40 consecutive days. On 41st day, the animals were sacrificed and brain sub regions namely, frontal cortex, corpus striatum, hippocampus and cerebellum were used to determine activities of anti-oxidant enzymes viz. Superoxide Dismutase (SOD), Catalase (CAT), Glutathione-Stransferase (GST), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) and levels of lipid peroxides using Thio-barbituric Acid Reactive Substance (TBARS) assay. Our investigation showed a significant decrease in SOD and CAT activity, whereas there occurred a decline in GST and GR activity with an increase in GPx activity to counteract the oxidative damage caused by significantly increased levels of lipid peroxides. The possible mechanism of this oxidative damage might be attributed to the production of sulphanilc acid as a metabolite in azofission of tartrazine. It may be concluded that the ADI levels of food azo dyes adversely affect and alter biochemical markers of brain tissue and cause oxidative damage.

Bioethical and Other Philosophical Considerations in Positive Psychiatry.

The paper begins by asserting the need for bioethical and related philosophical considerations in the emerging subspecialty Positive Psychiatry. Further discussion proceeds after offering operational definitions of the concepts fundamental to the field - Bioethics, Positive Psychology, Positive Psychiatry and Positive Mental Health - with their conceptual analysis to show their areas of connect and disconnect. It then studies the implications of positive and negative findings in the field, and presents the Positive Psychosocial Factors (PPSFs) like Resilience, Optimism, Personal Mastery, Wisdom, Religion/Spirituality, Social relationships and support, Engagement in pleasant events etc. It then evaluates them on the basis of the 4-principled bioethical model of Beneficence, Non-malfeasance, Autonomy and Justice (Beauchamp and Childress, 2009[5], 2013[6]), first offering a brief clarification of these principles and then their bioethical analysis based on the concepts of 'Common Morality', 'Specific Morality', 'Specification', 'Balancing' and 'Double Effects'. The paper then looks into the further development of the branch by studying the connectivity, synergy and possible antagonism of the various Positive Psychosocial Factors, and presents technical terms in place of common terms so that they carry least baggage. It also takes note of the salient points of caution and alarm that many incisive analysts have presented about further development in the related field of Positive Mental Health. Finally, the paper looks at where, and how, the field is headed, and why, if at all, it is proper it is headed there, based on Aristotle's concept of the four causes - Material, Efficient, Formal and Final. Suitable case vignettes are presented all through the write-up to clarify concepts.

Validation of the St. George's Respiratory Questionnaire in Nepal.

The St. George's Respiratory Questionnaire (SGRQ) is a standardized questionnaire for measuring impaired health and perceived well-being in chronic airway disease, but it is not available in the Nepali language. We translated the original SGRQ into Nepali and validated its use in 150 individuals aged 40 to 80 years with and without COPD.We also examined if the SGRQ could be used as a screening tool to identify individuals at risk for COPD. We translated the SGRQ following a standard protocol. The validation study was then conducted in both community and hospital-based settings in Nepal. We enrolled 100 participants from a community setting who were not actively seeking medical care, 50 of which met criteria for chronic obstructive pulmonary disease (COPD) (post-bronchodilator forced expiratory volume in 1 second [FEV1]/ forced vital capacity [FVC]<70%) and 50 who did not. We also enrolled 50 participants with an established diagnosis of COPD who attended outpatient pulmonary clinics. All participants completed the questionnaire. We used linear regressions to compare average SGRQ scores by disease status categories and by lung function values, adjusted for age, sex, height and body mass index (BMI).All 150 participants (mean age 59.8 years, 48% male, mean BMI 20.5 kg/m2) completed the SGRQ. In multivariable regression, the average SGRQ total score was 23.9 points higher in established cases of COPD and 18.1 points higher in community cases of COPD when compared to participants without COPD living in the community (all p<0.001). The SGRQ total score also increased by an average of 2.1 points for each 100 mL decrease in post-FEV1 (p<0.001). The area-under-the-curve for the SGRQ total score as a predictor of COPD was 0.77 (95% confidence interval [CI] 0.68 to 0.85) and the optimal cutoff to identify COPD was 33 points.We developed a Nepali-validated version of SGRQ, which correlated well with both disease status and severity.

Brain-mind dyad, human experience, the consciousness tetrad and lattice of mental operations: and further, the need to integrate knowledge from diverse disciplines.

Brain, Mind and Consciousness are the research concerns of psychiatrists, psychologists, neurologists, cognitive neuroscientists and philosophers. All of them are working in different and important ways to understand the workings of the brain, the mysteries of the mind and to grasp that elusive concept called consciousness. Although they are all justified in forwarding their respective researches, it is also necessary to integrate these diverse appearing understandings and try and get a comprehensive perspective that is, hopefully, more than the sum of their parts. There is also the need to understand what each one is doing, and by the other, to understand each other's basic and fundamental ideological and foundational underpinnings. This must be followed by a comprehensive and critical dialogue between the respective disciplines. Moreover, the concept of mind and consciousness in Indian thought needs careful delineation and critical/evidential enquiry to make it internationally relevant. The brain-mind dyad must be understood, with brain as the structural correlate of the mind, and mind as the functional correlate of the brain. To understand human experience, we need a triad of external environment, internal environment and a consciousness that makes sense of both. We need to evolve a consensus on the definition of consciousness, for which a working definition in the form of a Consciousness Tetrad of Default, Aware, Operational and Evolved Consciousness is presented. It is equally necessary to understand the connection between physical changes in the brain and mental operations, and thereby untangle and comprehend the lattice of mental operations. Interdisciplinary work and knowledge sharing, in an atmosphere of healthy give and take of ideas, and with a view to understand the significance of each other's work, and also to critically evaluate the present corpus of knowledge from these diverse appearing fields, and then carry forward from there in a spirit of cooperative but evidential and critical enquiry - this is the goal for this monograph, and the work to follow.

My close friends lurk all around the house, and he knows not!

Technology is a woman's best friend. Gadgets, appliances and contraception make life easy for the present day working woman. Men barely realize the importance of these even if they appear to agree to their use.

Humanity at the crossroads: does sri aurobindo offer an alternative?

In the light of Sri Aurobindo's philosophy, this paper looks into some of the problems of contemporary man as an individual, a member of society, a citizen of his country, a component of this world, and of nature itself. Concepts like Science; Nature,;Matter; Mental Being; Mana-purusa; Prana-purusa; Citta-purusa; Nation-ego and Nation-soul; True and False Subjectivism; World-state and World-union; Religion of Humanism are the focus of this paper. NATURE: Beneath the diversity and uniqueness of the different elements in Nature there is an essential unity that not only allows for this diversity but even supports it. Nature is both a benefactor and a force: a benefactor, because it acts to carry out the evolution of mankind; a force, because it also supplies the necessary energy and momentum to achieve it. NATURAL CALAMITIES: If mankind can quieten the tsunamis and cyclones and droughts and earthquakes that rage within, and behave with care and compassion towards Nature, not exploiting, denuding, or denigrating it, there is a strong possibility that Nature too will behave with equal care and compassion towards man and spare him the natural calamities than rend him asunder. SCIENCE: The limitation of science become obvious, according to Sri Aurobindo, when we realize that it has mastered knowledge of processes and helped in the creation of machinery but is ignorant of the foundations of being and, therefore, cannot perfect our nature or our life. SCIENCE AND PHILOSOPHY: The insights of philosophy could become heuristic and algorithmic models for scientific experimentation. MATTER: An interesting aspect of Sri Aurobindo's philosophy is his acceptance of the reality of matter even while highlighting its inadequacies; the ultimate goal, according to him, is the divination of matter itself. PURUSA: If the mana-purusa (mental being) were to log on to the genuine citta-purusa (psychic formation), without necessarily logging off from the prana-purusa (frontal formation), it may help quieten the turbulences within, which may be a prelude to the quietening of the disturbances without, whether it be physical maladies, cravings (for food, fame, fortune, etc.), destructive competitiveness; or wars, terrorism, ethnic conflicts, communal riots, and the other such social maladies that afflict mankind today. NATION-EGO (FALSE SUBJECTIVISM) AND NATION-SOUL (TRUE SUBJECTIVISM): Sri Aurobindo considers Nation-ego an example of false subjectivism, in which national identity and pride are stressed to prove one's superiority and suppress or exploit the rest. The Nation-soul, as an example of true subjectivism, attempts to capture one's traditional heritage and values in its pristine form, not as a reaction to hurts and angers or as compensation for real or imagined injuries or indignities of the past. WORLD-STATE (FALSE SUBJECTIVISM) AND WORLD-UNION (TRUE SUBJECTIVISM): Similarly, a World-state founded upon the principle of centralization and uniformity, a mechanical and formal unity, is an example of false subjectivism, while a World-union founded upon the principle of liberty and variation in a free and intelligent unity is an example of true subjectivism HUMAN ACTUALIZATION: Even if two human beings are similar, in so far as they are human beings, there is so much diversity between them. Part of the movement towards human self-actualization lies in the fact that this diversity should not be forcibly curbed, as also the realization that beneath all that appears disparate there is an essential unity. Also, man is not the end product of evolution but an intermediate stage between the animal and the divine. Moreover, he is endowed with consciousness that enables him to cooperate with the forces of evolution and speed up and telescope the next stage of evolution.

Notes on a few issues in the philosophy of psychiatry.

THE FIRST PART CALLED THE PREAMBLE TACKLES: (a) the issues of silence and speech, and life and disease; (b) whether we need to know some or all of the truth, and how are exact science and philosophical reason related; (c) the phenomenon of Why, How, and What; (d) how are mind and brain related; (e) what is robust eclecticism, empirical/scientific enquiry, replicability/refutability, and the role of diagnosis and medical model in psychiatry; (f) bioethics and the four principles of beneficence, non-malfeasance, autonomy, and justice; (g) the four concepts of disease, illness, sickness, and disorder; how confusion is confounded by these concepts but clarity is imperative if we want to make sense out of them; and how psychiatry is an interim medical discipline.THE SECOND PART CALLED THE ISSUES DEALS WITH: (a) the concepts of nature and nurture; the biological and the psychosocial; and psychiatric disease and brain pathophysiology; (b) biology, Freud and the reinvention of psychiatry; (c) critics of psychiatry, mind-body problem and paradigm shifts in psychiatry; (d) the biological, the psychoanalytic, the psychosocial and the cognitive; (e) the issues of clarity, reductionism, and integration; (f) what are the fool-proof criteria, which are false leads, and what is the need for questioning assumptions in psychiatry.The third part is called Psychiatric Disorder, Psychiatric Ethics, and Psychiatry Connected Disciplines. It includes topics like (a) psychiatric disorder, mental health, and mental phenomena; (b) issues in psychiatric ethics; (c) social psychiatry, liaison psychiatry, psychosomatic medicine, forensic psychiatry, and neuropsychiatry.The fourth part is called Antipsychiatry, Blunting Creativity, etc. It includes topics like (a) antipsychiatry revisited; (b) basic arguments of antipsychiatry, Szasz, etc.; (c) psychiatric classification and value judgment; (d) conformity, labeling, and blunting creativity.The fifth part is called The Role of Philosophy, Religion, and Spirituality in Psychiatry. It includes topics like (a) relevance of philosophy to psychiatry; (b) psychiatry, religion, spirituality, and culture; (c) ancient Indian concepts and contemporary psychiatry; (d) Indian holism and Western reductionism; (e) science, humanism, and the nomothetic-idiographic orientation.The last part, called Final Goal, talks of the need for a grand unified theory.The whole discussion is put in the form of refutable points.

Diseases of poverty and lifestyle, well-being and human development.

The problems of the haves differ substantially from those of the have-nots. Individuals in developing societies have to fight mainly against infectious and communicable diseases, while in the developed world the battles are mainly against lifestyle diseases. Yet, at a very fundamental level, the problems are the same-the fight is against distress, disability, and premature death; against human exploitation and for human development and self-actualisation; against the callousness to critical concerns in regimes and scientific power centres.While there has been great progress in the treatment of individual diseases, human pathology continues to increase. Sicknesses are not decreasing in number, they are only changing in type.The primary diseases of poverty like TB, malaria, and HIV/AIDS-and the often co-morbid and ubiquitous malnutrition-take their toll on helpless populations in developing countries. Poverty is not just income deprivation but capability deprivation and optimism deprivation as well.While life expectancy may have increased in the haves, and infant and maternal mortality reduced, these gains have not necessarily ensured that well-being results. There are ever-multiplying numbers of individuals whose well-being is compromised due to lifestyle diseases. These diseases are the result of faulty lifestyles and the consequent crippling stress. But it serves no one's purpose to understand them as such. So, the prescription pad continues to prevail over lifestyle-change counselling or research.The struggle to achieve well-being and positive health, to ensure longevity, to combat lifestyle stress and professional burnout, and to reduce psychosomatic ailments continues unabated, with hardly an end in sight.WE THUS REALISE THAT MORBIDITY, DISABILITY, AND DEATH ASSAIL ALL THREE SOCIETIES: the ones with infectious diseases, the ones with diseases of poverty, and the ones with lifestyle diseases. If it is bacteria in their various forms that are the culprit in infectious diseases, it is poverty/deprivation in its various manifestations that is the culprit in poverty-related diseases, and it is lifestyle stress in its various avatars that is the culprit in lifestyle diseases. It is as though poverty and lifestyle stress have become the modern "bacteria" of developing and developed societies, respectively.For those societies afflicted with diseases of poverty, of course, the prime concern is to escape from the deadly grip of poverty-disease-deprivation-helplessness; but, while so doing, they must be careful not to land in the lap of lifestyle diseases. For the haves, the need is to seek well-being, positive health, and inner rootedness; to ask science not only to give them new pills for new ills, but to define and study how negative emotions hamper health and how positive ones promote it; to find out what is inner peace, what is the connection between spirituality and health, what is well-being, what is self-actualisation, what prevents disease, what leads to longevity, how simplicity impacts health, what attitudes help cope with chronic sicknesses, how sicknesses can be reversed (not just treated), etc. Studies on well-being, longevity, and simplicity need the concerted attention of researchers.THE TASK AHEAD IS CUT OUT FOR EACH ONE OF US: physician, patient, caregiver, biomedical researcher, writer/journalist, science administrator, policy maker, ethicist, man of religion, practitioner of alternate/complementary medicine, citizen of a world community, etc. Each one must do his or her bit to ensure freedom from disease and achieve well-being.Those in the developed world have the means to make life meaningful but, often, have lost the meaning of life itself; those in the developing world are fighting for survival but, often, have recipes to make life meaningful. This is especially true of a society like India, which is rapidly emerging from its underdeveloped status. It is an ancient civilization, with a philosophical outlook based on a robust mix of the temporal and the spiritual, with vibrant indigenous biomedical and related disciplines, for example, Ayurveda, Yoga, etc. It also has a burgeoning corpus of modern biomedical knowledge in active conversation with the rest of the world. It should be especially careful that, while it does not negate the fruits of economic development and scientific/biomedical advance that seem to beckon it in this century, it does not also forget the values that have added meaning and purpose to life; values that the ancients bequeathed it, drawn from their experiential knowledge down the centuries.The means that the developed have could combine with the recipes to make them meaningful that the developing have. That is the challenge ahead for mankind as it gropes its way out of poverty, disease, despair, alienation, anomie, and the ubiquitous all-devouring lifestyle stresses, and takes halting steps towards well-being and the glory of human development.

Guidelines, editors, pharma and the biological paradigm shift.

Private investment in biomedical research has increased over the last few decades. At most places it has been welcomed as the next best thing to technology itself. Much of the intellectual talent from academic institutions is getting absorbed in lucrative positions in industry. Applied research finds willing collaborators in venture capital funded industry, so a symbiotic growth is ensured for both.There are significant costs involved too. As academia interacts with industry, major areas of conflict of interest especially applicable to biomedical research have arisen. They are related to disputes over patents and royalty, hostile encounters between academia and industry, as also between public and private enterprise, legal tangles, research misconduct of various types, antagonistic press and patient-advocate lobbies and a general atmosphere in which commercial interest get precedence over patient welfare.Pharma image stinks because of a number of errors of omission and commission. A recent example is suppression of negative findings about Bayer's Trasylol (Aprotinin) and the marketing maneuvers of Eli Lilly's Xigris (rhAPC). Whenever there is a conflict between patient vulnerability and profit motives, pharma often tends to tilt towards the latter. Moreover there are documents that bring to light how companies frequently cross the line between patient welfare and profit seeking behaviour.A voluntary moratorium over pharma spending to pamper drug prescribers is necessary. A code of conduct adopted recently by OPPI in India to limit pharma company expenses over junkets and trinkets is a welcome step.Clinical practice guidelines (CPG) are considered important as they guide the diagnostic/therapeutic regimen of a large number of medical professionals and hospitals and provide recommendations on drugs, their dosages and criteria for selection. Along with clinical trials, they are another area of growing influence by the pharmaceutical industry. For example, in a relatively recent survey of 2002, it was found that about 60% of 192 authors of clinical practice guidelines reported they had financial connections with the companies whose drugs were under consideration. There is a strong case for making CPGs based not just on effectivity but cost effectivity. The various ramifications of this need to be spelt out. Work of bodies like the Appraisal of Guidelines Research and Evaluation (AGREE) Collaboration and Guidelines Advisory Committee (GAC) are also worth a close look.Even the actions of Foundations that work for disease amelioration have come under scrutiny. The process of setting up 'Best Practices' Guidelines for interactions between the pharmaceutical industry and clinicians has already begun and can have important consequences for patient care. Similarly, Good Publication Practice (GPP) for pharmaceutical companies have also been set up aimed at improving the behaviour of drug companies while reporting drug trialsThe rapidly increasing trend toward influence and control by industry has become a concern for many. It is of such importance that the Association of American Medical Colleges has issued two relatively new documents - one, in 2001, on how to deal with individual conflicts of interest; and the other, in 2002, on how to deal with institutional conflicts of interest in the conduct of clinical research. Academic Medical Centers (AMCs), as also medical education and research institutions at other places, have to adopt means that minimize their conflicts of interest.Both medical associations and research journal editors are getting concerned with individual and institutional conflicts of interest in the conduct of clinical research and documents are now available which address these issues. The 2001 ICMJE revision calls for full disclosure of the sponsor's role in research, as well as assurance that the investigators are independent of the sponsor, are fully accountable for the design and conduct of the trial, have independent access to all trial data and control all editorial and publication decisions. However the findings of a 2002 study suggest that academic institutions routinely participate in clinical research that does not adhere to ICMJE standards of accountability, access to data and control of publication.There is an inevitable slant to produce not necessarily useful but marketable products which ensure the profitability of industry and research grants outflow to academia. Industry supports new, not traditional, therapies, irrespective of what is effective. Whatever traditional therapy is supported is most probably because the company concerned has a product with a big stake there, which has remained a 'gold standard' or which that player thinks has still some 'juice' left.Industry sponsorship is mainly for potential medications, not for trying to determine whether there may be non-pharmacological interventions that may be equally good, if not better. In the paradigm shift towards biological psychiatry, the role of industry sponsorship is not overt but probably more pervasive than many have realised, or the right thinking may consider good, for the health of the branch in the long run.An issue of major concern is protection of the interests of research subjects. Patients agree to become research subjects not only for personal medical benefit but, as an extension, to benefit the rest of the patient population and also advance medical research.We all accept that industry profits have to be made, and investment in research and development by the pharma industry is massive. However, we must also accept there is a fundamental difference between marketing strategies for other entities and those for drugs.The ultimate barometer is patient welfare and no drug that compromises it can stand the test of time. So, how does it make even commercial sense in the long term to market substandard products? The greatest mistake long-term players in industry may make is try to adopt the shady techniques of the upstart new entrant. Secrecy of marketing/sales tactics, of the process of manufacture, of other strategies and plans of business expansion, of strategies to tackle competition are fine business tactics. But it is critical that secrecy as a tactic not extend to reporting of research findings, especially those contrary to one's product.Pharma has no option but to make a quality product, do comprehensive adverse reaction profiles, and market it only if it passes both tests.Why does pharma adopt questionable tactics? The reasons are essentially two:What with all the constraints, a drug comes to the pharmacy after huge investments. There are crippling overheads and infrastructure costs to be recovered. And there are massive profit margins to be maintained. If these were to be dependent only on genuine drug discoveries, that would be taking too great a risk.Industry players have to strike the right balance between profit making and credibility. In profit making, the marketing champions play their role. In credibility ratings, researchers and paid spokes-persons play their role. All is hunky dory till marketing is based on credibility. When there is nothing available to make for credibility, something is projected as one and marketing carried out, in the calculated hope that profits can accrue, since profit making must continue endlessly. That is what makes pharma adopt even questionable means to make profits.Essentially, there are four types of drugs. First, drugs that work and have minimal side-effects; second, drugs which work but have serious side-effects; third, drugs that do not work and have minimal side-effects; and fourth, drugs which work minimally but have serious side-effects. It is the second and fourth types that create major hassles for industry. Often, industry may try to project the fourth type as the second to escape censure.The major cat and mouse game being played by conscientious researchers is in exposing the third and fourth for what they are and not allowing industry to palm them off as the first and second type respectively. The other major game is in preventing the second type from being projected as the first. The third type are essentially harmless, so they attract censure all right and some merriment at the antics to market them. But they escape anything more than a light rap on the knuckles, except when they are projected as the first type.What is necessary for industry captains and long-term players is to realise:Their major propelling force can only be producing the first type. 2. They accept the second type only till they can lay their hands on the first. 3. The third type can be occasionally played around with to shore up profits, but never by projecting them as the first type. 4. The fourth type are the laggards, real threat to credibility and therefore do not deserve any market hype or promotion.In finding out why most pharma indulges in questionable tactics, we are lead to some interesting solutions to prevent such tactics with the least amount of hassles for all concerned, even as both profits and credibility are kept intact.

The connection between academia and industry.

The growing commercialization of research with its effect on the ethical conduct of researchers, and the advancement of scientific knowledge with its effect on the welfare or otherwise of patients, are areas of pressing concern today and need a serious, thorough study. Biomedical research, and its forward march, is becoming increasingly dependent on industry-academia proximity, both commercial and geographic. A realization of the commercial value of academic biomedical research coupled with its rapid and efficient utilization by industry is the major propelling force here. A number of well-intentioned writers in the field look to the whole development with optimism. But this partnership is a double-edged sword, for it carries with it the potential of an exciting future as much as the prospect of misappropriation and malevolence. Moreover, such partnerships have sometimes eroded public trust in the research enterprise itself.Connected to the growing clout of industry in institutions is concern about thecommercialization of research and resolving the 'patient or product' loyalty.There is ambivalence about industry funding and influence in academia, and a consequent 'approach-avoidance' conflict. If academia has to provide the patients and research talent, industry necessarily has to provide the finances and other facilities based on it. This is an invariable and essential agreement between the two parties that they can walk out of only at their own peril. The profound ethical concerns that industry funded research has brought center-stage need a close look, especially as they impact patients, research subjects, public trust, marketability of products, and research and professional credibility.How can the intermediate goal of industry (patient welfare) serve the purpose of the final goal of academia is the basic struggle for conscientious research institutions /associations. And how best the goal of maximizing profits can be best served, albeit suitably camouflaged as patient welfare throughout, is the concern of the pharmaceutical industry.A very great potential conflict of interest lies in the fact that academia needs the sophisticated instruments that only big funding can provide, while at the same time resists the attempts of the fund provider to set the agenda of research, protocol, design, publication, the works. Conflicts arise at many steps and levels of functioning, and are related to the expectations, competing interests, and conflicting priorities of the different entities involved, whether they are the academic medical centers, the funding agencies, the patients and their families, or the investors and venture capitalists.The public expects access to new treatments. Its appetite for innovation has been bolstered by the constant attention given by the press to new treatments and by the implicit promise from researchers of continuing advances. Similarly, patients demand privacy and control over information about themselves.It makes greater sense for genuine researchers to associate with large long-term industry players who have a track record of genuine hard-core discoveries, even if the process is slow (maybe), and the funding less (may not be).The element of control venture capitalists exert over the pharmaceutical industry is an under researched area for obvious reasons. But it needs further probing, for that will lay bare the pulls and pressures under which industry works.It makes sense for ethically minded researchers and institutions not to fall in the trap of stocks and equity investments in industry, howsoever attractive they appear, and get rid of them as soon as possible if they have them. If at all they want, it makes more sense to own stocks of larger well established concerns, for the stock upheavals being less, the pressure of the market-place, and of venture sharks, is likely to be lower too.While active participation by the researcher in the commercialization process may be greatly desired by industry, ostensibly in the name of creating value, academia must realize it is a bait it might find hard to swallow in the long run. It makes more sense for the researcher and institution to forego such temptations and/or walk out of such investments as soon as possible.While mainstream medicine and research are booming, as is connected industry, concerns about professional commitment to patient welfare are growing too. Increasing corporate influence is challenging certain long held and fundamental values of patient care, which will have far reaching implications for biomedical care and the future progress of mainstream medicine.

Public welfare agenda or corporate research agenda?

As things stand today, whether we like it or not, industry funding is on the upswing. The whole enterprise of medicine in booming, and it makes sense for industry to invest more and more of one's millions into it. The pharmaceutical industry has become the single largest direct funding agency of medical research in countries like Canada, the United Kingdom and the United States.Since the goals of industry and academia differ, it seems that conflicts of interest are inevitable at times. The crucial decision is whether the public welfare agenda of academia, or the corporate research agenda of industry, should occupy center stage when they conflict.There is enough evidence to show that funding by industry is very systematic, and results that are supportive of the safety and efficacy of sponsor's products alone get the funds. It is no surprise, therefore, that one finds very few negative drug trials reports published, and whatever are, are likely to be by rival companies to serve their commercial interests.Renewed and continued funding by industry decides the future prospects of many academic researchers. At the same time there is now evidence that pharmaceutical companies attempt suppression of research findings, may be selective in publishing results, and may delay or stymie publication of unfavourable results. This is a major area of concern for all conscientious researchers and industry watchers.Industry commonly decides which clinical research/trial gets done, not academia, much though the latter may wish to believe otherwise. It finds willing researchers to carry this out. This can be one area of concern. Another area of pressing concern is when industry decides to both design and control publication of research.It makes sense for researchers to refuse to allow commercial interests to rule research reporting. Research having been reported, the commercial implications of such reporting is industry's concern. But, doctoring of findings to suit commerce is to be resisted at all costs. In this even pliant researchers need have no fear, for if they indeed publish what will work, the concerned sponsor will benefit in the long run. The only decision academia has to make is refuse to comply with predestined conclusions of sponsors for the 'thirty pieces of silver'. Instead do genuine research and make sixty for themselves.The useful rule of thumb is: Keep the critical antenna on, especially with regard to drug trials, and more especially their methodology, and study closely the conflict of interest disclosed, and if possible undisclosed, before you jump on the band wagon to herald the next great wonder drug.There are three important lessons to be learnt by academia in all academia-industry relationships:i)LESSON NUMBER ONE: incorporate the right to publish contrary findings in the research contract itself. Which means, it makes great sense for academia to concentrate on the language and contractual provisions of sponsored research, to read the fine print very closely, and protect their research interests in case of conflict.ii)LESSON NUMBER TWO: a number of lawsuits successfully brought up against industry recently reflect earnest attempts by patient welfare bodies and others to remedy the tilt. It will result in a newfound confidence in academia that augurs well for academia industry relationship in the long run. Hence the second lesson for academia: do not get browbeaten by threats of legal actioniii)LESSON NUMBER THREE: Academia should keep itself involved right from inception of the clinical trial through to ultimate publication. And this must be an integral part of the written contract.The time to repeat cliches about the exciting future of the academia-industry connect is past. A concerted effort to lay a strong foundation of the relationship on practical ethical grounds has become mandatory.

Medicine as a corporate enterprise, patient welfare centered profession, or patient welfare centered professional enterprise?

There is an alarming trend in the field of medicine, whose portents are ominous but do not seem to shake the complacency and merry making doing the rounds.The wants of the medical man have multiplied beyond imagination. The cost of organizing conferences is no longer possible on delegate fees. The bottom-line is: Crores for a Conference Millions for a Mid-Term. However, the problem is that sponsors keep a discreet but careful tab on docs. All in all, costs of medicines escalate, and quality medical care becomes a luxury. The whole brunt of this movement is borne by the patient.Companies like GlaxoSmithKline, Bayer, Pfizer, Bristol-Myers Squibb, AstraZeneca, Schering-Plough, Abbott Labs, TAP Pharmaceuticals, Wyeth and Merck have paid millions of dollars each as compensation in the last few years. The financial condition of many pharmaceutical majors is not buoyant either. Price deflation, increased Rand D spending, and litigation costs are the main reasons. In the future, the messy lawsuits situation would no longer be restricted to industry. It would involve academia and practising doctors as well. Indian pharma industry captains, who were busy raking in the profits at present, would also come under the scanner. If nothing else, it means industry and docs will have to sit down and do some soul searching.Both short and long-term measures will have to be put into place. Short-term measures involve reduction in i) pharma spending over junkets and trinkets; ii) hype over 'me too' drugs; iii) manipulation of drug trials; iv) getting pliant researchers into drug trials; iv) manipulation of Journal Editors to publish positive findings about their drug trials and launches; v) and for Indian Pharma, to conduct their own unbiased clinical trial of the latest drug projected as a blockbuster in the West, before pumping in their millions.The long-term measures are related to the way biomedical advance is to be charted. We have to decide whether medicine is to become a corporate enterprise or remain a patient welfare centered profession. A third approach involves an eclectic resolution of the two. Such amount of patient welfare as also ensures profit, and such amount of profit as also ensures patient welfare is to be forwarded. For, profit, without patient welfare, is blind. And patient welfare, without profit, is lame. According to this approach, medicine becomes a patient welfare centered professional enterprise.The various ramifications of each of these approaches are discussed in this monograph.