Monday, June 7, 2010
Tuesday, May 25, 2010
Monday, April 12, 2010
Monday, February 22, 2010
ETHICS ON TRIAL
(Frontline Magazine -
Volume 27 - Issue 01 :: Jan. 02-15, 2010 FRONTLINE
PUBLIC HEALTH
Ethics on trial
This article is based on a major expose of an unethical drug trial conducted on patients of the Regional Cancer Centre at Thiruvananthapuram by a researcher from Johns Hopkins University in the United States. The original reports and interviews, by R. KRISHNAKUMAR, appeared in the issues of Frontline published between August 2001 and December 2005.
THE elements of the controversial ‘Johns Hopkins-RCC drug trial’ are now well known: a U.S.-based biology professor with a potential anti-cancer “drug” discovery and links with a “start-up” pharmaceutical company; an American university holding a patent for the experimental drug; an international real-estate businessman willing to invest millions in the new company for further development of the drug through human trials; a contract research organisation that scouts worldwide for opportunities to do clinical research using the drug; and a medical institution in a Third World country eager to conduct the trials on its patients for them.
Clinical drug trials involve ethical minefields. It was in mid-2001 that a whistleblower radiotherapist at the Regional Cancer Centre (RCC) in Thiruvananthapuram startled India by claiming that the authorities of the reputed hospital had subjected unsuspecting oral cancer patients to an experiment, injecting untested, potentially unsafe chemicals into their tumours, as part of an international research project that sought to develop new cancer drugs.
The chemicals, known briefly as M4N and G4N, were synthetic derivatives of a plant product that could arrest the growth of artificially induced tumours in mice, as a biology professor, Dr Ru Chih C. Huang, and her team had demonstrated earlier in her laboratory at the U.S.-based Johns Hopkins University.
The first human trials of M4N and G4N were indeed conducted between November 1999 and April 2000 at the RCC following an agreement signed “on behalf of Hopkins” by Dr Huang (the lead inventor) and the cancer centre authorities led by its then Director, Dr M. Krishnan Nair.
Among the 27 patients, some were administered the potentially more risky chemical G4N, either separately or along with M4N. Though all of them were made to sign “consent papers”, the patients thought the injections were part of their treatment, and were not properly informed of the risks involved.
A few days later, after four or five doses of M4N and/or G4N were administered to them, the tumours were surgically removed and the injected tissue samples were sent to Hopkins. The patients were sent home after the surgery and radiotherapy or chemotherapy in some cases, and there was no real follow-up on whether the injections had adversely affected them. The U.S. researchers, however, soon reported that the injected tumour samples had shown “signs of shrinking and dying”.
Barely two months after the trials ended in India, in June 2000, a Singapore-based real-estate businessman (and banker) Ang Tiong Loi visited the JHU and promised to invest millions of dollars for the development of effective anti-cancer drugs from the new compounds.
It was also announced that the investment would enable “a new company” to conduct further research, “including FDA-approved clinical trials”, using the new compounds, which had already been tested on Indian patients. Hopkins held the patent for the new compounds and claimed they would soon prove to be “wonderful cancer drugs” that would bring returns to the university and the investor.
But ethically sound research involving human participants must satisfy a number of globally accepted requirements. It must be subjected to a prior review by an ethics review committee, minimise risk to the participants, obtain voluntary and informed consent of individual participants, and ensure the risks involved are reasonable when compared with potential benefits. Moreover, the research must be non-exploitative, be essential, show equal regard for all subjects, ensure equitable distribution of the burdens and the benefits, take adequate care to compensate participants for injuries sustained directly during research and be accountable and transparent, among other things.
But the RCC’s “collaborative venture” with non-medical researchers of the Johns Hopkins University to test M4N and G4N in human cancers clearly failed to prevent the abuse of research subjects or show concern for their safety.
S. MAHINSHA
The Regional Cancer Centre in Thiruvananthapuram.
While the RCC authorities continued to deny the allegations that came in the wake of the tests, Frontline published a series of investigative reports from November 2001 unravelling the funding, business connections and conflict of interests in the Hopkins-RCC trials, the flouting of safety and ethical norms, and the plight of the 27 patients, all of whom were discharged soon after the experiment. A number of them died within a few months or never visited the hospital again.
One of them, 65-year-old M. Gopalan from Tirupur in Tamil Nadu, (who later approached the State Human Rights Commission and had his complaint rejected on technical grounds) told Frontline in an interview in 2001, a few months before he died: “Nearly a fortnight before the scheduled surgery in January 2000, I was asked to ‘go to another room’ in the hospital and ‘sign on a piece of paper’. I did not understand a word of what was written on the paper as it was in Malayalam, the local language. Anyway, I signed it, thinking that it was routine procedure before surgery. Then, two doctors, not the ones who were treating me regularly, examined the burning lump on my tongue. They squeezed it, and then they gave me a painful injection. More injections followed, almost at the same place, the same unbearable way. Then the injected lump was removed. The doctors said I was cured and then they sent me home....
“But I was not cured. When I came back with another lump on my tongue, my doctor asked me one day why I had allowed them to give me those injections and why I had failed to inform him about it. I asked him, ‘Didn’t I give you my trust?’ I thought it was part of my treatment.”
Would he have volunteered had they told him that it was an experiment? Did he know that it involved risks unknown even to the researchers? Was he aware it was the first time the chemicals were being injected on human beings to try and find a cure for his type of cancer? Did he know he could refuse to be part of the experiment?
He replied: “Do you think anybody would take such a risk? Who would have thought they would do such a thing to me?” (As reported first in Aug. 2001.)
The treatment data were never revealed, and subsequently the RCC authorities also began to fudge the figures. The partial data from the case-sheets of patients released by the RCC in 2001 at the beginning of the controversy too give room for uneasy conclusions (‘Trial and Errors’, Dec. 16, 2005). Data on only 23 patients were released, though the RCC itself had acknowledged earlier that 27 patients were involved. Later, the doctors began to discuss results of just 18 patients. There was no evidence to show that all the 27 patients had been monitored after the injections, specifically to understand the effect of the injected drugs on them.
Thereafter, in what was alleged to be “a sham government inquiry” a one-man commission (Dr. Parvesh Parikh of the Tata Memorial Hospital in Mumbai) concluded “all patients were fine”. But later, in a telephone conversation, Parikh disclosed to Frontline that he had examined only “10 or 11” of the 27 patients involved in the trial. As the then Union Health Minister explained to Frontline, the government had the duty to protect “the reputation of an institution offering treatment to thousands of people”.
Thus, even though the patients were exposed to unknown risks without their voluntary or informed consent, because of the overriding, and perhaps convenient, concern of the State and Central governments “to save the reputation of the RCC”, the drug trial collaborators were left to pretend that “except perhaps for some procedural irregularities” no harm was done to the patients and the trials were conducted in an above-board clinical setting (Frontline, December 7, 2001).
Subsequently, in 2005, when the controversy seemed to have died down with no action being taken against the erring doctors, an audacious attempt was made by some of the RCC physicians involved to whitewash their deeds and claim credit for concocted claims about the trial. Some of them began to publish papers at international medical conferences stating that the trials at the RCC had been a grand success and that the patients had shown “relapse-free survival even at five years”.
The report of Frontline’s inquiry into this claim was published in December 2005, proving their lies and with exclusive new disclosures about the unsuccessful bid that had continued in the U.S. to develop a cancer drug out of M4N, with help from the biopsy results of the RCC trials and brushing aside the ethical, moral and legal questions that were being raised in India.
S. GOPAKUMAR
M. Gopalan from Tirupur in Tamil Nadu, one of the patients on whom the 'anti-cancer drug' was tested by RCC doctors and who filed a complaint before the State Human Rights Commission regarding the therapy. A 2001 picture.
A spokesperson of Erimos Pharmaceuticals, the start-up company that was conducting further human trials of M4N in the U.S., Jennifer C. Stern, told Frontline in an interview that the Erimos clinical programme “would not have occurred” without the safety and effectiveness clinical information provided by the Huang-Krishnan Nair study at the RCC. She also said that the early development work conducted in India, “prior to Erimos taking over the development programme, provided invaluable support information on the potential clinical usefulness of EM-1421, as well as its lack of systemic effects” (those that involve many organs or the whole body).
Significantly, the G4N human trials were not held in the U.S. and, despite the trial data from the RCC, the researchers were allowed to launch human trials using M4N in the U.S. only after further trials with the chemical were conducted in animals there. What was becoming clear in 2005 was that drug development from the two controversial chemicals was not going smoothly in the U.S. too, with the principal investigator of a Phase I study conducted at one of the three centres too reporting extreme adverse (M4N) drug reactions in the trial participants.
A January 2005 newsletter of the U.S.-based human rights organisation CIRCARE quoted the results from this adverse study as cited in the Journal of Clinical Oncology (Vol 22, No 148 July 15 Supplement 2004:5614) and said: “Far from being not toxic in humans, of a total of three subjects enrolled in Dunphy’s (Dr F.R. Dunphy of a North Carolina cancer centre) trial, one subject was removed from the study after developing a tracheal-cutaneous fistula [essentially a hole extending from the windpipe through the skin of the neck], a second patient required hospitalisation twice upon developing heart-block – both of which were presumably adverse drug reactions – and all patients experienced pain, severe enough to require intravenous morphine relief. According to public statements given out by the RCC in Kerala, India, however, none of the research subjects contacted suffered any adverse events, complications, or harm upon receiving intra-tumoral injection of the same investigational drug. Such statements strain credulity in the light of Dunphy’s recent data.” (Frontline, December 16, 2005).
Interestingly, between July 27, 2001, when the Hopkins authorities first announced through Frontline that the trials at RCC “had not been authorised by any department of the university”, and 2005, when Frontline’s reinvestigation took place, Dr Huang and her university had clearly tried to distance themselves from the controversy and any responsibility for the RCC trials.
Even as early as November 2001, soon after an internal inquiry, the university had tried to build a legal wall between itself and the RCC clinical trials by saying that Huang had no authority to sign the agreement on its behalf. It maintained that merely because the university cut a cheque it did not mean it had authorised the trials. Hopkins consistently disowned the trials at the RCC even though its own inquiry had found they were done by a Hopkins professor without adequate safety testing on animals, without a proper Institutional Review Board (IRB) review and with chemicals developed at its own Biology Department.
Dr Huang got away with a mild punishment barring her from being the “principal investigator on any future research project involving human subjects”. Asked how she could claim that there was no harm done to the patients in India when indeed there was no evidence of continuous monitoring of the patients at the RCC, she told Frontline: “I am not clinically involved with the follow-up of these patients. You would need to direct that question to the appropriate [RCC] physician” (interview with Dr Huang, December 16, 2005).
She and the Hopkins spokesperson Dennis O’Shea also explained to Frontline that there was no basis for the claims made by the RCC authorities that the drug when developed would get a “joint patent”, “profits would be shared equally” and “if it is given to a drug company, as is usually done, the RCC would get 50 per cent of the royalty”.
“The gains from the RCC trial were, from the very beginning, meant to be shared by Johns Hopkins University, its scientists, the company they floated and the Singapore millionaire who is sponsoring it. For them, it was merely a question of finding a gold mine and being very quick about it. It is a fairly accepted principle that you should not do research on people who would not benefit from the product of that research. The people of India, at whose expense they got the preliminary encouraging results, would not benefit at all,” Dr C.R. Soman, former chairman of the activist organisation ‘Health Action by People’, commented in Frontline in 2005.
Over 35 interviews were conducted as part of Frontline’s investigation into the Hopkins-RCC drug trial controversy from 2001 to 2005, with doctors, researchers and authorities of the RCC and Hopkins, administrators, professors, historians, experts in medical ethics, representatives of non-governmental organisations (NGOs), hospital staff, inquiry and ethics committee members, media correspondents, government officials, regulatory authorities, pharmaceutical company representatives, Ministers and politicians in India and the U.S.
Their disclosures eventually turned out to be the incremental elements in a classic jigsaw case of conflict of interests involved in clinical trials sponsored by international drug researchers in developing countries.
The most significant outcome of the controversy and the disclosures that followed was an increase in public awareness in India about clinical trials and the effect of unseen, market-driven forces that threaten the safety of the patients involved and taunt the objectivity of investigators and the scientific integrity of clinical trials.
"Ethics on trial"
"A response from Johns Hopkins"
Drug trials and Ethics
The changing creed
Claims and contradictions
"Clinical trials should promote health care": Interview with Dr.M.S.Valiathan
The misuse of science
The truth of the drug trials
"Complying with established policy": Interview with Hopkins spokesperson Dennis O'Shea
Trial and errors
"Erimos has broadened the research": Interview with Hopkins biology professor Dr. Ru Chih C. Huang
A case of betrayal
An award and some claims
"Hopkins is committed to acting ethically, legally and morally": Interview with Hopkins spokesperson Dennis O'Shea
(http://www.frontlineonnet.com/fl2701/stories/20100115270109000.htm)
Volume 27 - Issue 01 :: Jan. 02-15, 2010 FRONTLINE
PUBLIC HEALTH
Ethics on trial
This article is based on a major expose of an unethical drug trial conducted on patients of the Regional Cancer Centre at Thiruvananthapuram by a researcher from Johns Hopkins University in the United States. The original reports and interviews, by R. KRISHNAKUMAR, appeared in the issues of Frontline published between August 2001 and December 2005.
THE elements of the controversial ‘Johns Hopkins-RCC drug trial’ are now well known: a U.S.-based biology professor with a potential anti-cancer “drug” discovery and links with a “start-up” pharmaceutical company; an American university holding a patent for the experimental drug; an international real-estate businessman willing to invest millions in the new company for further development of the drug through human trials; a contract research organisation that scouts worldwide for opportunities to do clinical research using the drug; and a medical institution in a Third World country eager to conduct the trials on its patients for them.
Clinical drug trials involve ethical minefields. It was in mid-2001 that a whistleblower radiotherapist at the Regional Cancer Centre (RCC) in Thiruvananthapuram startled India by claiming that the authorities of the reputed hospital had subjected unsuspecting oral cancer patients to an experiment, injecting untested, potentially unsafe chemicals into their tumours, as part of an international research project that sought to develop new cancer drugs.
The chemicals, known briefly as M4N and G4N, were synthetic derivatives of a plant product that could arrest the growth of artificially induced tumours in mice, as a biology professor, Dr Ru Chih C. Huang, and her team had demonstrated earlier in her laboratory at the U.S.-based Johns Hopkins University.
The first human trials of M4N and G4N were indeed conducted between November 1999 and April 2000 at the RCC following an agreement signed “on behalf of Hopkins” by Dr Huang (the lead inventor) and the cancer centre authorities led by its then Director, Dr M. Krishnan Nair.
Among the 27 patients, some were administered the potentially more risky chemical G4N, either separately or along with M4N. Though all of them were made to sign “consent papers”, the patients thought the injections were part of their treatment, and were not properly informed of the risks involved.
A few days later, after four or five doses of M4N and/or G4N were administered to them, the tumours were surgically removed and the injected tissue samples were sent to Hopkins. The patients were sent home after the surgery and radiotherapy or chemotherapy in some cases, and there was no real follow-up on whether the injections had adversely affected them. The U.S. researchers, however, soon reported that the injected tumour samples had shown “signs of shrinking and dying”.
Barely two months after the trials ended in India, in June 2000, a Singapore-based real-estate businessman (and banker) Ang Tiong Loi visited the JHU and promised to invest millions of dollars for the development of effective anti-cancer drugs from the new compounds.
It was also announced that the investment would enable “a new company” to conduct further research, “including FDA-approved clinical trials”, using the new compounds, which had already been tested on Indian patients. Hopkins held the patent for the new compounds and claimed they would soon prove to be “wonderful cancer drugs” that would bring returns to the university and the investor.
But ethically sound research involving human participants must satisfy a number of globally accepted requirements. It must be subjected to a prior review by an ethics review committee, minimise risk to the participants, obtain voluntary and informed consent of individual participants, and ensure the risks involved are reasonable when compared with potential benefits. Moreover, the research must be non-exploitative, be essential, show equal regard for all subjects, ensure equitable distribution of the burdens and the benefits, take adequate care to compensate participants for injuries sustained directly during research and be accountable and transparent, among other things.
But the RCC’s “collaborative venture” with non-medical researchers of the Johns Hopkins University to test M4N and G4N in human cancers clearly failed to prevent the abuse of research subjects or show concern for their safety.
S. MAHINSHA
The Regional Cancer Centre in Thiruvananthapuram.
While the RCC authorities continued to deny the allegations that came in the wake of the tests, Frontline published a series of investigative reports from November 2001 unravelling the funding, business connections and conflict of interests in the Hopkins-RCC trials, the flouting of safety and ethical norms, and the plight of the 27 patients, all of whom were discharged soon after the experiment. A number of them died within a few months or never visited the hospital again.
One of them, 65-year-old M. Gopalan from Tirupur in Tamil Nadu, (who later approached the State Human Rights Commission and had his complaint rejected on technical grounds) told Frontline in an interview in 2001, a few months before he died: “Nearly a fortnight before the scheduled surgery in January 2000, I was asked to ‘go to another room’ in the hospital and ‘sign on a piece of paper’. I did not understand a word of what was written on the paper as it was in Malayalam, the local language. Anyway, I signed it, thinking that it was routine procedure before surgery. Then, two doctors, not the ones who were treating me regularly, examined the burning lump on my tongue. They squeezed it, and then they gave me a painful injection. More injections followed, almost at the same place, the same unbearable way. Then the injected lump was removed. The doctors said I was cured and then they sent me home....
“But I was not cured. When I came back with another lump on my tongue, my doctor asked me one day why I had allowed them to give me those injections and why I had failed to inform him about it. I asked him, ‘Didn’t I give you my trust?’ I thought it was part of my treatment.”
Would he have volunteered had they told him that it was an experiment? Did he know that it involved risks unknown even to the researchers? Was he aware it was the first time the chemicals were being injected on human beings to try and find a cure for his type of cancer? Did he know he could refuse to be part of the experiment?
He replied: “Do you think anybody would take such a risk? Who would have thought they would do such a thing to me?” (As reported first in Aug. 2001.)
The treatment data were never revealed, and subsequently the RCC authorities also began to fudge the figures. The partial data from the case-sheets of patients released by the RCC in 2001 at the beginning of the controversy too give room for uneasy conclusions (‘Trial and Errors’, Dec. 16, 2005). Data on only 23 patients were released, though the RCC itself had acknowledged earlier that 27 patients were involved. Later, the doctors began to discuss results of just 18 patients. There was no evidence to show that all the 27 patients had been monitored after the injections, specifically to understand the effect of the injected drugs on them.
Thereafter, in what was alleged to be “a sham government inquiry” a one-man commission (Dr. Parvesh Parikh of the Tata Memorial Hospital in Mumbai) concluded “all patients were fine”. But later, in a telephone conversation, Parikh disclosed to Frontline that he had examined only “10 or 11” of the 27 patients involved in the trial. As the then Union Health Minister explained to Frontline, the government had the duty to protect “the reputation of an institution offering treatment to thousands of people”.
Thus, even though the patients were exposed to unknown risks without their voluntary or informed consent, because of the overriding, and perhaps convenient, concern of the State and Central governments “to save the reputation of the RCC”, the drug trial collaborators were left to pretend that “except perhaps for some procedural irregularities” no harm was done to the patients and the trials were conducted in an above-board clinical setting (Frontline, December 7, 2001).
Subsequently, in 2005, when the controversy seemed to have died down with no action being taken against the erring doctors, an audacious attempt was made by some of the RCC physicians involved to whitewash their deeds and claim credit for concocted claims about the trial. Some of them began to publish papers at international medical conferences stating that the trials at the RCC had been a grand success and that the patients had shown “relapse-free survival even at five years”.
The report of Frontline’s inquiry into this claim was published in December 2005, proving their lies and with exclusive new disclosures about the unsuccessful bid that had continued in the U.S. to develop a cancer drug out of M4N, with help from the biopsy results of the RCC trials and brushing aside the ethical, moral and legal questions that were being raised in India.
S. GOPAKUMAR
M. Gopalan from Tirupur in Tamil Nadu, one of the patients on whom the 'anti-cancer drug' was tested by RCC doctors and who filed a complaint before the State Human Rights Commission regarding the therapy. A 2001 picture.
A spokesperson of Erimos Pharmaceuticals, the start-up company that was conducting further human trials of M4N in the U.S., Jennifer C. Stern, told Frontline in an interview that the Erimos clinical programme “would not have occurred” without the safety and effectiveness clinical information provided by the Huang-Krishnan Nair study at the RCC. She also said that the early development work conducted in India, “prior to Erimos taking over the development programme, provided invaluable support information on the potential clinical usefulness of EM-1421, as well as its lack of systemic effects” (those that involve many organs or the whole body).
Significantly, the G4N human trials were not held in the U.S. and, despite the trial data from the RCC, the researchers were allowed to launch human trials using M4N in the U.S. only after further trials with the chemical were conducted in animals there. What was becoming clear in 2005 was that drug development from the two controversial chemicals was not going smoothly in the U.S. too, with the principal investigator of a Phase I study conducted at one of the three centres too reporting extreme adverse (M4N) drug reactions in the trial participants.
A January 2005 newsletter of the U.S.-based human rights organisation CIRCARE quoted the results from this adverse study as cited in the Journal of Clinical Oncology (Vol 22, No 148 July 15 Supplement 2004:5614) and said: “Far from being not toxic in humans, of a total of three subjects enrolled in Dunphy’s (Dr F.R. Dunphy of a North Carolina cancer centre) trial, one subject was removed from the study after developing a tracheal-cutaneous fistula [essentially a hole extending from the windpipe through the skin of the neck], a second patient required hospitalisation twice upon developing heart-block – both of which were presumably adverse drug reactions – and all patients experienced pain, severe enough to require intravenous morphine relief. According to public statements given out by the RCC in Kerala, India, however, none of the research subjects contacted suffered any adverse events, complications, or harm upon receiving intra-tumoral injection of the same investigational drug. Such statements strain credulity in the light of Dunphy’s recent data.” (Frontline, December 16, 2005).
Interestingly, between July 27, 2001, when the Hopkins authorities first announced through Frontline that the trials at RCC “had not been authorised by any department of the university”, and 2005, when Frontline’s reinvestigation took place, Dr Huang and her university had clearly tried to distance themselves from the controversy and any responsibility for the RCC trials.
Even as early as November 2001, soon after an internal inquiry, the university had tried to build a legal wall between itself and the RCC clinical trials by saying that Huang had no authority to sign the agreement on its behalf. It maintained that merely because the university cut a cheque it did not mean it had authorised the trials. Hopkins consistently disowned the trials at the RCC even though its own inquiry had found they were done by a Hopkins professor without adequate safety testing on animals, without a proper Institutional Review Board (IRB) review and with chemicals developed at its own Biology Department.
Dr Huang got away with a mild punishment barring her from being the “principal investigator on any future research project involving human subjects”. Asked how she could claim that there was no harm done to the patients in India when indeed there was no evidence of continuous monitoring of the patients at the RCC, she told Frontline: “I am not clinically involved with the follow-up of these patients. You would need to direct that question to the appropriate [RCC] physician” (interview with Dr Huang, December 16, 2005).
She and the Hopkins spokesperson Dennis O’Shea also explained to Frontline that there was no basis for the claims made by the RCC authorities that the drug when developed would get a “joint patent”, “profits would be shared equally” and “if it is given to a drug company, as is usually done, the RCC would get 50 per cent of the royalty”.
“The gains from the RCC trial were, from the very beginning, meant to be shared by Johns Hopkins University, its scientists, the company they floated and the Singapore millionaire who is sponsoring it. For them, it was merely a question of finding a gold mine and being very quick about it. It is a fairly accepted principle that you should not do research on people who would not benefit from the product of that research. The people of India, at whose expense they got the preliminary encouraging results, would not benefit at all,” Dr C.R. Soman, former chairman of the activist organisation ‘Health Action by People’, commented in Frontline in 2005.
Over 35 interviews were conducted as part of Frontline’s investigation into the Hopkins-RCC drug trial controversy from 2001 to 2005, with doctors, researchers and authorities of the RCC and Hopkins, administrators, professors, historians, experts in medical ethics, representatives of non-governmental organisations (NGOs), hospital staff, inquiry and ethics committee members, media correspondents, government officials, regulatory authorities, pharmaceutical company representatives, Ministers and politicians in India and the U.S.
Their disclosures eventually turned out to be the incremental elements in a classic jigsaw case of conflict of interests involved in clinical trials sponsored by international drug researchers in developing countries.
The most significant outcome of the controversy and the disclosures that followed was an increase in public awareness in India about clinical trials and the effect of unseen, market-driven forces that threaten the safety of the patients involved and taunt the objectivity of investigators and the scientific integrity of clinical trials.
"Ethics on trial"
"A response from Johns Hopkins"
Drug trials and Ethics
The changing creed
Claims and contradictions
"Clinical trials should promote health care": Interview with Dr.M.S.Valiathan
The misuse of science
The truth of the drug trials
"Complying with established policy": Interview with Hopkins spokesperson Dennis O'Shea
Trial and errors
"Erimos has broadened the research": Interview with Hopkins biology professor Dr. Ru Chih C. Huang
A case of betrayal
An award and some claims
"Hopkins is committed to acting ethically, legally and morally": Interview with Hopkins spokesperson Dennis O'Shea
(http://www.frontlineonnet.com/fl2701/stories/20100115270109000.htm)
Saturday, February 13, 2010
The Mind in the Modern Medicine
It is curious that the mind, so important at the turn of the 20th century, is experiencing today a reawakening in scientific and societal consciousness. The founders of modern medical science in the 18th and 19th centuries had clearly conceived the mind to be a representation of the brain; people like Alois Alzheimer demonstrated pathological abnormalities in the brain of people affected with dementia. Indeed, centuries earlier, the father of modern medicine, Hippocrates, had firmly placed “our joys, sorrows, desires and feelings” in the brain.
Sigmund Freud, who started his career as a neurologist, developed an interest in the mind while a student of the legendary neurologist Charcot in Paris. Charcot was deeply interested in hysteria, that condition where physical symptoms like fainting, seizures and paralysis are expressed due to an abnormal emotional state, rather than an abnormal physical state. Many aspiring neurologists of the time including Freud were attracted to Paris by Charcot’s knowledge and erudition.
Sigmund Freud, however, branched off from Charcot to develop his own hypothesis of the human mind, in what famously became the school of psychoanalysis. Freud took the exploration of the mind in hysterical states deeper, into areas that few physicians before him had dared to tread. His theory of “consciousness” attempted to explain the role of deep-rooted emotional conflicts originating in early life, in developing symptoms of the mind later on. Freudian thought is complex, requiring many hours of concerted study. In a nutshell, Freud proposed that the human tendency was to repress anxiety provoking emotional conflicts that the conscious mind could not possibly contemplate. While these thoughts were confined to the unconscious mind, there were, inevitably, times when they emerged into the conscious, and given their unacceptable nature manifested (were converted into) a physical symptom, instead. Freudian thought spawned a school of psychoanalysis which dominated the practice of “psychological medicine” for over a century. However, his all-pervasive view of sexual underpinnings for all manner of emotional conflict, for example the Oedipus complex where the mother is the inappropriate object of sexual attention of the male child, was not accepted in its totality by his contemporaries.
Two milestones in the latter half of the twentieth century brought the mind firmly back into the realm of brain science. The first, the discovery of the neuroleptic drug chlorpromazine that could control effectively the symptoms of serious mental illness like schizophrenia, followed on by a range of psychotropic drugs with potential to address a range of other emotional symptoms, provided indirect evidence that the brain had a role in the development and manifestation of human emotions. The second, the development of several dynamic brain-imaging tools in the last two decades of the twentieth century and the first decade of the twenty-first, has transformed our understanding of the human brain and mind, permitting us to visualise live, brain activity during a psychological task.
Crossroads
The brain and mind interface is therefore at an interesting crossroads in modern medicine. There is a growing understanding in medical science of the role our brains play in determining what are predominantly emotional symptoms. Research, for example, has shown that people with psychopathic personalities, hitherto considered to suffer from a disorder of the mind, have a poor perception of others’ facial emotions, and experience difficulties in affect recognition (that is, gauging the other person’s mood). These abnormalities in perception have been linked to abnormalities in brain function, the amygdala, part of the emotional brain, being implicated in many instances. Clearly, as our ability to image the mind expands, so will our understanding of brain-mind relationships and knowledge of “how the mind works!”
From a social and health policy perspective, the mind has assumed considerable importance. In a seminal paper, “The Mental Wealth of Nations,” published in Nature (Volume 455; October 23, 2008), Beddington and colleagues emphasise that countries must learn to capitalise on their citizens’ cognitive resources if they are to prosper, both economically and socially, and that early interventions for emotional health and cognition will be the key to prosperity. Reporting the Foresight Project on Mental Capital and Wellbeing commissioned by the U.K. Government Office for Science, they introduce two important concepts. Mental capital encompasses both cognitive and emotional resources. It includes people’s cognitive ability; their flexibility and efficiency at learning; and their emotional intelligence, or social skills and resilience in the face of stress. Mental well-being, on the other hand, refers to individuals’ ability to develop their potential, work productively and creatively, build strong and positive relationships with others and contribute to their community. The importance of detecting mental disorders early, the role of science, for example neural markers for childhood learning disability; the development of early interventions that enhance mental capital and mental well-being, boosting brain power through the lifespan; and encouragement for processes that will help people adapt well to the changing needs of the workplace, as also engage in life-long learning, are highlighted here.
From a clinical practice perspective, the importance of mental health, wellness and health-related quality of life as outcome indicators of both physical and mental disorders is becoming widely accepted. The view is that it is not enough to heal the body of a person affected with physical disease; it is also crucial that we heal the mind, enhancing wellness, is gaining credence in modern medicine, quality of life having become established as the best outcome of treatment. Indeed, the reintegration of people into society as they recover from illness requires as an imperative the restoration of both their mental capital and mental well-being.
Pray, what is the status of hysteria, that original symptom of the mind, in this era of modern medicine, you may well ask. It is noteworthy that a whole range of bodily symptoms that have no physical basis — tension headache and chronic fatigue, atypical facial pain, atypical chest pain, irritable bowels and bladder, fibromyalgia, burning in the private parts, to name just a few — all have their putative origins in the theory of hysterical conversion. It is estimated that between 20 per cent and 35 per cent of all primary care consultations and about a fifth of all emergency room visits are for physical symptoms such as these, that do not have a physical basis. They are also responsible for the loss of many patient and caregiver workdays; untold suffering and burdensome expense, both personal and social; and unnecessary investigations in pursuit of that elusive diagnosis.
Physicians who frequently encounter these symptoms have learnt to spot the telltale signs that are their forerunner: multiple consultations (doctor shopping); the large bag filled with a variety of investigation reports that have mysteriously failed to identify “anything wrong”; the constant need for reassurance, combined curiously with disbelief in the doctor’s opinion, notwithstanding his erudition; the development of new symptoms, without any apparent physical basis, soon after old ones disappear; disenchantment with the medical profession for failing to diagnose, sometimes even subtle pride in being “such a difficult diagnostic dilemma”; as indeed the failure of any serious setback to manifest itself despite months, sometimes years, of ongoing symptoms… the list of diagnostic clues is endless.
The French physician Briquet described this syndrome which for many years carried his name. In modern medicine this ailment goes by the name “Somatisation Disorder.” And in the clinic setting, in an era of advancing diagnostic technology, it has become the most common manifestation of hysteria. Indeed, somatisation, thought to be more common in non-western cultures with traditionally limited verbal expression of emotions, is almost becoming fashionable, akin to “swooning” (another hysterical symptom) in the Victorian era.
Hysteria does therefore exemplify the importance of the mind in modern medicine. It may well have origins in the brain, which future research may reveal: it clearly is a significant public health problem that does affect mental capital and well-being; it does pose a tremendous drain on the public exchequer and private resources; it has potential for cure through early diagnosis and intervention; and interestingly, may well be the last frontier to traverse at the interface between the brain and mind.
( Dr. Ennapadam S. Krishnamoorthy is Honorary Secretary & T.S. Srinivasan Chair in Clinical Neurosciences and Health Policy, Voluntary Health Services. E-mail: esk@nsig.org)
http://beta.thehindu.com/opinion/lead/article105233.ece?homepage=true
Tuesday, February 2, 2010
Christopher Reeve, stem cell research activist; Cord Blood banking
1) http://archives.cnn.com/2001/ALLPOLITICS/07/29/reeve.cnna/index.html
2)
Cord Blood: Biological Insurance
by Usha Raman
"The miracle is not just your baby. It's what comes attached." The large vinyl hoarding is hard to miss as one drives through the glass-and-concrete-tower-lined western pocket of 'Cyberabad' known as Hi-Tech City. This part of the city is populated by young techies and their young families, couples just about to embark on parenthood, a sub-section of the population that lives by and with high technology.
The high-tech advertised on the hoarding refers to an exciting area of medicine that has fascinated biologists and biotechnologists for a couple of decades now - regenerative medicine. Specifically, it sells the idea of cord blood banking - harvesting and storing the blood that is retained in the umbilical cord after the birth of a baby. "This blood is rich in haemopoetic stem cells - proliferative cells that have the capacity to develop into blood cells," explains Dr Geeta Vemuganti, a scientist who works in the stem cell laboratory at L V Prasad Eye Institute, Hyderabad. "There are also indications that these cells may have the capacity to develop into other kinds of lineages, such as nerve cells or cardiac tissue."
So what does all this have to do with prospective parents? Known sources of stem cells are adult bone marrow, peripheral blood to some extent, embryos and umbilical cord blood. The use of human embryos for therapeutic or research purposes is fraught with ethical and legal problems. The availability of adult bone marrow is dependent on voluntary donations and the possibilities of tissue matching are very low. Besides, it has been found that cord blood is some 10 times richer than bone marrow in its proportion of haemopoetic stem cells. Such cells have primarily been used to treat blood disorders, such as some forms of leukaemia, thalassemia and other blood malignancies.
Cord blood is harvested immediately after the child is born. The blood that remains in the umbilical cord before the placenta is discarded is harvested and immediately transported to a storage facility, where it is stored in liquid nitrogen at below -186 degrees Celsius. This can be used in case the child - or a sibling or other family member - develops a condition that requires stem cell therapy.
Research indicates that these cells remain viable in storage for up to 18 years, and some suggest, even 21 years.
"When a couple decides to bank the cord blood at the time of childbirth, they are in a way taking biological insurance for their child," says K P Rajendra, Centre Head, LifeCell, one of the first private cord blood banking companies in the country. The advertising and other promotional measures have certainly caught the imagination of young couples in Hyderabad.
"We have about 30 prospective mothers registering with us every month in Hyderabad alone," he says. This 'biological insurance' costs couples close to Rs.60,000, with LifeCell now offering a variety of part-payment options.
Farha Raju is one of the young mothers who decided to go in for the service. "My parents had heard about it, and it seemed like it was not that much to pay for something that might be useful in the future," she says. Raju and her family asked her obstetrician about it, and she referred them to LifeCell. The one concern Raju had was the quality of storage and processing, "since we had read that these were crucial to the viability of the cells." Once she was convinced on this count, there was no looking back.
However, the aggressive marketing is something that clients as well as the medical community are not entirely comfortable with. "Their representatives would call us at all hours; it was quite a hard sell," says Raju.
The literature too is more promotional than scientific, often quite emotional, suggesting that cord blood could provide more solutions than is actually borne out by research. "Much stem cell research is in the pre-clinical stage," says Vemuganti. While cord blood has been successfully used to treat blood malignancies, it has yet to be used to regenerate other organs.
"Besides, the chances of a person actually needing to use it are extremely low," notes Dr Evita Fernandez, a gynecologist with a successful practice in Hyderabad. Thirty of her patients have gone in for cord blood banking in the past nine months. It is estimated that an individual's chances of using personal cord blood for blood disorders before the age of 20 - the limit of the cells' viability - is very low; around 1 in 2,700. "What they are offering is a promise - and a promise is just that," quips Vemuganti.
Transparency in processes and procedures is another issue that concerns the medical community. "After the few bad experiences we've had with in-vitro fertilization, where we've heard rumors of semen samples being switched and so on, practitioners tend to be wary of private companies that sell such technologies," says Fernandez.Dr K Gayathri, a haemotologist with a special interest in inherited blood disorders, agrees.
"Everyone is a bit wary of private ventures." She feels that there tends to be a lack of transparency in the industry in general, and while this may not relate specifically to cord blood banking, there is a definite lack of comfort with such activities, "because of the history in our country, especially". This general lack of trust, combined with a low level of awareness about new technologies, leads to a situation where few medical practitioners champion these new services. "There's such a resource crunch in general; most doctors are fighting even for basic amenities in their nursing homes. They don't really want to spend time learning about new areas - and stem cell therapy is kind of esoteric," says Gayathri.
As a result, companies like LifeCell spend considerable resources and time convincing medical practitioners to refer patients. Some doctors, however, feel there is a thin line between 'educating' the medical fraternity and 'persuading' them through means such as fees for referrals. While most do not have a quarrel with the technology itself, they do worry about the cost and the ultimate benefit to the patient.
A scientific advisory paper published by the London-based Royal College of Obstetricians and Gynecologists notes that while cord blood banking offers definite advantages, compared to say bone marrow, in terms of availability, tissue matching, lower rates of transmitted infections and other graft-related problems. It says, however, that the debate should shift to the need for public rather than for-profit or private cord blood banking.
In Europe, professional bodies actively discourage private banking and instead recommend publicly funded cord blood banks that collect voluntary donations.
"Cord blood is such an easily available resource, and most mothers would have no issues with donating something that is otherwise discarded," says Gayathri.
With the low likelihood of a donor requiring the blood for personal use - and the relative ease of finding matches for those who do require stem cell therapy - it makes sense for cord blood to become a community resource, much like bone marrow registries in the US and Europe, which are available to anyone in the world. "It could be like a blood bank - no one pays for the blood; it is a common resource," says Vemuganti. She also feels that the availability of a voluntary, community bank would encourage more research into the actual potential of cord blood stem cells - thus taking us beyond a mere promise.
August 27, 2006
By arrangement with Women's Feature Service
2)
Cord Blood: Biological Insurance
by Usha Raman
"The miracle is not just your baby. It's what comes attached." The large vinyl hoarding is hard to miss as one drives through the glass-and-concrete-tower-lined western pocket of 'Cyberabad' known as Hi-Tech City. This part of the city is populated by young techies and their young families, couples just about to embark on parenthood, a sub-section of the population that lives by and with high technology.
The high-tech advertised on the hoarding refers to an exciting area of medicine that has fascinated biologists and biotechnologists for a couple of decades now - regenerative medicine. Specifically, it sells the idea of cord blood banking - harvesting and storing the blood that is retained in the umbilical cord after the birth of a baby. "This blood is rich in haemopoetic stem cells - proliferative cells that have the capacity to develop into blood cells," explains Dr Geeta Vemuganti, a scientist who works in the stem cell laboratory at L V Prasad Eye Institute, Hyderabad. "There are also indications that these cells may have the capacity to develop into other kinds of lineages, such as nerve cells or cardiac tissue."
So what does all this have to do with prospective parents? Known sources of stem cells are adult bone marrow, peripheral blood to some extent, embryos and umbilical cord blood. The use of human embryos for therapeutic or research purposes is fraught with ethical and legal problems. The availability of adult bone marrow is dependent on voluntary donations and the possibilities of tissue matching are very low. Besides, it has been found that cord blood is some 10 times richer than bone marrow in its proportion of haemopoetic stem cells. Such cells have primarily been used to treat blood disorders, such as some forms of leukaemia, thalassemia and other blood malignancies.
Cord blood is harvested immediately after the child is born. The blood that remains in the umbilical cord before the placenta is discarded is harvested and immediately transported to a storage facility, where it is stored in liquid nitrogen at below -186 degrees Celsius. This can be used in case the child - or a sibling or other family member - develops a condition that requires stem cell therapy.
Research indicates that these cells remain viable in storage for up to 18 years, and some suggest, even 21 years.
"When a couple decides to bank the cord blood at the time of childbirth, they are in a way taking biological insurance for their child," says K P Rajendra, Centre Head, LifeCell, one of the first private cord blood banking companies in the country. The advertising and other promotional measures have certainly caught the imagination of young couples in Hyderabad.
"We have about 30 prospective mothers registering with us every month in Hyderabad alone," he says. This 'biological insurance' costs couples close to Rs.60,000, with LifeCell now offering a variety of part-payment options.
Farha Raju is one of the young mothers who decided to go in for the service. "My parents had heard about it, and it seemed like it was not that much to pay for something that might be useful in the future," she says. Raju and her family asked her obstetrician about it, and she referred them to LifeCell. The one concern Raju had was the quality of storage and processing, "since we had read that these were crucial to the viability of the cells." Once she was convinced on this count, there was no looking back.
However, the aggressive marketing is something that clients as well as the medical community are not entirely comfortable with. "Their representatives would call us at all hours; it was quite a hard sell," says Raju.
The literature too is more promotional than scientific, often quite emotional, suggesting that cord blood could provide more solutions than is actually borne out by research. "Much stem cell research is in the pre-clinical stage," says Vemuganti. While cord blood has been successfully used to treat blood malignancies, it has yet to be used to regenerate other organs.
"Besides, the chances of a person actually needing to use it are extremely low," notes Dr Evita Fernandez, a gynecologist with a successful practice in Hyderabad. Thirty of her patients have gone in for cord blood banking in the past nine months. It is estimated that an individual's chances of using personal cord blood for blood disorders before the age of 20 - the limit of the cells' viability - is very low; around 1 in 2,700. "What they are offering is a promise - and a promise is just that," quips Vemuganti.
Transparency in processes and procedures is another issue that concerns the medical community. "After the few bad experiences we've had with in-vitro fertilization, where we've heard rumors of semen samples being switched and so on, practitioners tend to be wary of private companies that sell such technologies," says Fernandez.Dr K Gayathri, a haemotologist with a special interest in inherited blood disorders, agrees.
"Everyone is a bit wary of private ventures." She feels that there tends to be a lack of transparency in the industry in general, and while this may not relate specifically to cord blood banking, there is a definite lack of comfort with such activities, "because of the history in our country, especially". This general lack of trust, combined with a low level of awareness about new technologies, leads to a situation where few medical practitioners champion these new services. "There's such a resource crunch in general; most doctors are fighting even for basic amenities in their nursing homes. They don't really want to spend time learning about new areas - and stem cell therapy is kind of esoteric," says Gayathri.
As a result, companies like LifeCell spend considerable resources and time convincing medical practitioners to refer patients. Some doctors, however, feel there is a thin line between 'educating' the medical fraternity and 'persuading' them through means such as fees for referrals. While most do not have a quarrel with the technology itself, they do worry about the cost and the ultimate benefit to the patient.
A scientific advisory paper published by the London-based Royal College of Obstetricians and Gynecologists notes that while cord blood banking offers definite advantages, compared to say bone marrow, in terms of availability, tissue matching, lower rates of transmitted infections and other graft-related problems. It says, however, that the debate should shift to the need for public rather than for-profit or private cord blood banking.
In Europe, professional bodies actively discourage private banking and instead recommend publicly funded cord blood banks that collect voluntary donations.
"Cord blood is such an easily available resource, and most mothers would have no issues with donating something that is otherwise discarded," says Gayathri.
With the low likelihood of a donor requiring the blood for personal use - and the relative ease of finding matches for those who do require stem cell therapy - it makes sense for cord blood to become a community resource, much like bone marrow registries in the US and Europe, which are available to anyone in the world. "It could be like a blood bank - no one pays for the blood; it is a common resource," says Vemuganti. She also feels that the availability of a voluntary, community bank would encourage more research into the actual potential of cord blood stem cells - thus taking us beyond a mere promise.
August 27, 2006
By arrangement with Women's Feature Service
Subscribe to:
Posts (Atom)