Monday, January 31, 2011

A prescription for prayer?

Is prayer an effective and important element in a person’s healing process? Can the prayers of a priest in an American diocese or a rabbi at Jerusalem’s Western Wall really influence the health of a cancer patient in a Dublin hospital?

A new international study of healing prayer, which suggests that prayer for another person's healing just might help, has re-opened the debate on the hotly contested question: can prayer heal?

Investigators in the latest US-led study say a crucial difference between their research and previous studies in this area is its key focus on proximity – the person praying is physically near the person being prayed for. This, they claim, could make all the difference.

The new research, titled "Study of the Therapeutic Effects of Proximal Intercessory Prayer (STEPP) on Auditory and Visual Impairments in Rural Mozambique," measured surprising improvements in vision and hearing after Proximal Intercessory Prayer (PIP) was administered.

"We found a statistically significant effect of PIP for the population of both those with auditory and visual impairments," says study lead author Dr Candy Gunther Brown, an associate professor in the Department of Religious Studies at Indiana University in Bloomington. "We didn't generally find that people who were totally deaf or blind to start with ended up with 20/20 vision and perfect hearing, but those with moderate to severe impairments when tested before the intervention, had a much, much improved threshold."

Scientific research on intercessory prayer has in recent decades generated a firestorm of controversy, with critics charging that attempts to study the efficacy of prayer are inherently unscientific and should be abandoned because the mechanisms are poorly understood and too complex to measure. Not surprisingly, several research efforts have produced contradictory findings.

The title of the current study makes reference to the widely discussed 2006 "STEP" (study of the therapeutic effects of intercessory prayer) research, led by the renowned Dr Herbert Benson of Harvard Medical School, which evaluated the impact of such prayer on patients recovering from coronary artery bypass graft surgery. It concluded that prayer itself had no effect, but certainty of receiving prayer adversely affected health.

However, Dr Gunther Brown points out that the STEP study, like most previous research on the healing power of prayer, focused on distant intercessory prayer (DIP) rather than proximal prayer.

"If empirical research continues to indicate that PIP may be therapeutically beneficial, then - whether or not the mechanisms are adequately understood - there are ethical and non-partisan public policy reasons to encourage further related research," she urges. "It is a primary privilege and responsibility of medical science to pursue a better understanding of therapeutic inventions that may advance global health, especially in contexts where conventional medical treatments are inadequate or unavailable.”

Dr Candy Gunther Brown
Dr Gunther Brown’s research is published in the September 2010 issue of the Southern Medical Journal. She and her colleagues studied the activities of the healing groups Iris Ministries and Global Awakening in Mozambique and Brazil because of their reputation as hotspots of specialised prayer for those with hearing and vision impairments.

The researchers used an audiometer and vision charts to evaluate 14 rural Mozambican subjects who reported impaired hearing, and 11 who reported impaired vision, both before and after the subjects received PIP. The study focused on hearing and vision because it is possible to measure them with an audiometer and vision charts, allowing a more direct measure of improvement than simply asking people whether they feel better.

Subjects exhibited improved hearing and vision that was statistically significant after PIP was administered. Two subjects with impaired hearing reduced the threshold at which they could detect sound by 50 decibels. Three subjects had their tested vision improve from 20/400 or worse to 20/80 or better.

Dr Gunther Brown recounts that one subject, an elderly Mozambican woman named Maryam, could not see two fingers held up just one foot in front of her when she arrived for a Pentecostal prayer intervention in her village. Nor could she see the eye chart from a similarly close distance.

But after a healer at the evangelical meeting laid hands on her and prayed for less than a minute, Maryam was able to not only see the five fingers held up in front of her but could count them as well. The eye chart also came into view, with Maryam able to read down to the 20/125 line.

Supplemental digital content for the published study reports on a follow-up study with similar findings conducted by the same researchers in urban Brazil.

While Dr Gunther Brown doesn’t discount that some of the results may stem from a placebo effect, the magnitude of measured effects exceeds that reported in previous suggestion and hypnosis studies.

She has observed that many people who turn to divine healing also try "holistic" approaches such as chiropractic, acupuncture, yoga, homeopathy, and Reiki. "When people are sick," she remarks, "many look for healing wherever they can find it. They really don't care about philosophical or theological consistency."

Irish bio-ethicist Dr Donal O'Mathuna has explored this issue in great detail, conducting a thorough review of research into the healing power of prayer for a book he co-authored on “Alternative Medicine” for the Christian Medical Association in the US.

Although one might not immediately associate prayer with the myriad of complementary medical therapies available, Dr O’Mathuna says it is one of the most frequently reported alternative treatments used.

Several prominent surveys, led by Professor of Medicine David Eisenburg, Harvard Medical School, which examined trends in alternative medicine use in the US, repeatedly found that prayer was by far the most commonly reported alternative therapy, as defined by the researchers.

“Yet they would then leave that out of their overall conclusion because, if they incorporated that statistic, they would effectively be saying that about 85 percent of Americans use alternative medicine,” says Dr O'Mathuna, who is Senior Lecturer in Ethics, Decision-Making & Evidence in the School of Nursing, Dublin City University.

“I think the recent interest in the healing power of prayer has arisen in part because when you define alternative medicine as broadly as is has been defined, prayer falls into that definition. But the traditional secular or non-religious approach to medicine, as it has become, would prefer not to deal with the issue of spiritual and sacred prayer.

“Medicine is very scientific and prayer for healing is both very difficult to define and very difficult to measure, and yet it is so important with the general public. More important with the patients than perhaps secular medicine wants to acknowledge or is aware of.”

Dr Donal O'Mathuna
Dr O'Mathuna points out that research on prayer is not a recent phenomenon. In 1872, Carlow native John Tyndall, a professor in London, proposed having all Christians pray for patients in a particular hospital for a number of years. Tyndall was sceptical of prayer's efficacy and anticipated no differences in health outcomes.

Although his proposed experiment was never carried out, it created much controversy, raising methodological, theological and ethical concerns that still apply today. One response published by Sir Francis Galton, a cousin of Charles Darwin, boldly observed that royalty and clergy, for whom a long life is frequently prayed for, had shorter life expectancies than other gentry or professionals.

During the course of researching his book, Dr O'Mathuna identified approximately 30 scientific studies on prayer for healing conducted over the last couple of decades. But he remarks that, on closer examination, from a methodological perspective, many of these suffer from some clear limitations.

Dr Benson’s STEP study, along with a number of other research endeavours in this area, examined the efficacy of different prayer approaches from various religious traditions by combining the different types together.

“To me, this is a really weak way to design scientific research; it’s like trying to study the effectiveness of a drug but doctors can administer it in which ever way they feel like, and at what ever dose they want.

“Other researchers have taken a different approach and used a particular prayer from a particular religious tradition. For example, the first most significant study was a high-quality, randomised controlled trial published in 1988 by Dr Randolph Byrd, who used only born again Christians practicing daily devotional prayer and actively involved in Christian fellowship. He evaluated the effects of distant intercessory prayer in about 400 coronary care unit patients.

“But Byrd had 27 or so different outcomes that they measured to see whether or not there was a difference between the intercessory prayer group or a control group. This is another methodological minefield because the more measures you use, the greater the possibility that, just by pure chance, you find significant differences between the groups.

“Byrd found in some of the results that there was a significant difference but in the majority of measurements there wasn’t a difference. Of course, when the study was picked up, the press tended to focus on those significant improvements but left out the fact that there were many results that didn’t find any difference.

“From a methodological point of view, you would want to have one or two specific primary outcomes and they should be the focus as to whether there is a significant difference.”

Of those prayer studies that adopted this approach, Dr O'Mathuna’s says that only one showed dramatic improvements in the prayed for group, compared to the control group. The controversial findings, published in the September 2001 issue of the Journal of Reproductive Medicine, revealed that a group of women who had people praying for them had a 50 percent pregnancy rate compared to a 26 percent rate in the group of women who did not have people praying for them. None of the women undergoing the IVF procedures knew about the praying.

However, this hopelessly flawed Columbia University “miracle” study has since been discredited. Critics of the study question its methodology - involving several "tiers" of people, some praying for the study subjects and others praying that the prayers would be effective - as well as the fact that no informed consent was obtained.

Since its publication, the lead author, Dr Rogerio Lobo, has withdrawn his name from the paper, ostensibly because of his limited relationship to the study. Furthermore, co-author Daniel Wirth, a lawyer who designed and allegedly conducted the study, was sentenced in November 2004 to five years in prison after pleading guilty to conspiracy to commit mail and bank fraud. FBI papers filed during the case also show that Wirth has used a series of false identities over the years. And in February 2007, the third author, Dr Kwang Cha was charged with plagiarism of a study he published in 2005.

“Although there is nothing conclusive to show that the results of this study are fraudulent, there are huge question marks over its methodology and the credibility of the authors,” Dr O'Mathuna offers.

Commenting on the new STEPP research, examining proximal intercessory prayer, he highlights the absence of a control group as an obvious disadvantage. “That’s going to suffer from the limitations of any before and after study. They may show real differences in a person’s life but they’re not going to be able to show what the causes of those differences were.”

However, he adds: “To me [the STEPP] study confirms the importance that medicine is a relational professional. Of course the doctor or surgeon’s skill is very important, but for medicine to really heal people you need to have the whole relational, personal aspect taken care of. Whether it’s the surgeon or the nurse at the bedside, family members or community to take care of those needs, all of that is what these types of studies are confirming.

“From a Christian perspective, clinical trials cannot control for the intervention of God to heal patients in one study group or the other. Also the Bible teaches that God may answer prayers, not by granting a healing but by giving the patient greater strength and greater faith.

“Perhaps, if prayer research could measure the outcomes of people's ability to deal with illness and tragedy, we could expect significantly positive results.

The people behind the studies of prayer and healing

Dr Wendy Cadge
A novel social history of intercessory prayer studies has suggested that these clinical investigations actually say more about the scientists conducting the studies than about the power of prayer to heal.

Collectively, this 2009 analysis of four decades of prayer studies provides a fascinating snapshot of changing religious demographics, evolving ideas about the relationship between religion and medical science, and the development of the clinical trial as the gold standard of biomedical research.

"I do not know why physicians and scientists conducted these studies," said the research author and Brandeis University sociologist Wendy Cadge, an expert on the intersection of religion and medicine in contemporary American society, "but personal religious beliefs appear to have played a role, along with curiosity."

The earliest studies undertaken in the sixties were based exclusively on Protestant prayers, while more recent studies, reflecting growing social awareness of other religions, combine Christian, Jewish, Buddhist and other prayers, Dr Cadge observed.

"With double blind clinical trials, scientists tried their best to study something that may be beyond their best tools," she said, "and reflects more about them and their assumptions than about whether prayer 'works.'"

Reflecting a recent shift toward de-legitimising studies of intercessory prayer, recent commentators in the medical literature concluded: "We do not need science to validate our spiritual beliefs, as we would never use faith to validate our scientific data."

The healing power of prayer

Unlike medical practitioners in the East, many physicians in the West argue that the healing power of science is far superior to, and often incompatible with, the healing power of prayer. This is not the view of Dr Larry Dossey, one of the world's foremost authorities on the synergy of physical health and spiritual awareness, and former chief of staff of Medical City Dallas Hospital.

Dr Dossey has penned several books on the health benefits of prayer and spirituality. His 1993 New York Times Bestseller, Healing Words, details the enormous body of data showing, he claims, that the act of prayer can greatly affect the practice of medicine. Prayer can help with high blood pressure, asthma, heart attacks, headaches, and anxiety, he writes. Moreover, it could alter enzyme activity, blood cell growth, and the germination of seeds.

In his 1999 book, Reinventing Medicine, Dr Dossey presents a compelling argument for merging awareness of consciousness into the practice of modern medicine.

He contends that we are entering an era of the "non-local mind" - that consciousness can accomplish healing outside the confines of one's brain and body, influencing distant events, people and circumstances. He does not discount the efficacy of medical intervention so much as he anticipates an enlightened model of partnership between patient and healer.

Popular spirituality author and medical doctor Deepak Chopra maintains that prayer experiments are supporting what he's been saying all along: There are healing forces in nature that science is only beginning to understand.

He remarks: "At the moment, I would agree that some of these studies are tentative, that we should be cautious in the way we interpret the results. But the studies are encouraging enough that we should pursue them, because if we don't, we may have missed one of the most amazing phenomena in nature."

Wednesday, January 26, 2011

Building bridges for tomorrow’s medicine

More than 16,000 new cases of cancer are diagnosed in Ireland each year. Despite aggressive treatment, for some of these patients, current cancer therapies will not enough to save their lives. But there is hope on the horizon. Buzzwords like “translational research”, “personalised medicine” and “smart drugs” now form part of a more optimistic lexicon describing new potential for effective, targeted approaches to cancer therapy.
Translational medical science is an exciting and rapidly evolving domain, and no where more so than in cancer research, which is now reaping the benefits of the translational approach to research. The primary goal of “translational” research is to integrate discoveries in the laboratory with clinical trials and observational studies in hospital and outpatient settings - taking pioneering developments more rapidly from the “bench-to-bedside”.

A team approach
A central strength is that translational research has fostered extensive cooperation between basic researchers, clinical investigators and the pharmaceutical industry. In cancer medicine, this broad-based partnership is generating many new and innovative, targeted treatments that work more effectively and with less toxicity.
This emerging field presents a promising future for cancer medicine, not only in terms of discovering potential cures, but also developing new diagnostic and prognostic tools as well as less toxic therapies that could add decades to a cancer patient’s life.
All Irish universities now have state of the art biosciences and translational research centres which integrate with the clinical research centres in Irish hospitals. For example, Molecular Medicine Ireland links five medical schools and their associated academic hospitals in a partnership that translates “eureka’ events in the lab into improved diagnostics and therapies for patients.

A driving force behind many of the Irish translational cancer research endeavours is ICORG - the All-Ireland Co-operation Oncology Research Group. ICORG is a national network of over 400 clinical and laboratory-based cancer researchers which has built up an enviable international research reputation over the last 13 years, securing affiliations with some of world’s leading cancer research centres and companies in the US and Europe engaged in clinical and translational cancer research.
In so doing, ICORG has also secured very early access for Irish cancer patients to the latest and most novel therapeutics available anywhere in the world.
For instance, ICORG is playing a pivotal role in the development and evaluation of a new test which may permit the individualisation of treatment of early stage (Node negative, estrogen receptor positive) breast cancer. This TAILORx trial has recently completed a global enrolment of over 11,000 breast cancer patients with the largest single recruitment site being in Ireland.
The study is evaluating the ability of a revolutionary new 21 gene test, called Oncotype Dx, to predict and distinguish patients who are likely to need more aggressive therapy from those who’s cancer is unlikely to spread and can therefore be saved the toxicity and side effects of this form of treatment.
Due to the huge clinical and patient interest in this molecular-based diagnostic tool and the diagnostic value of the test, a leading Irish insurance company announced late last year that it would cover the €3,180 test cost in all of its health insurance plans.

At the interface of basic and clinical research
Dr Robert O’Connor
“There’s no question that translational medicine is really the only way forward now in identifying better treatments and diagnostic tools for cancer, and our clinicians and scientists in Ireland are very active in this field,” confirms Dr Robert O’Connor, who is Biological Science lecturer and a Senior Programme Leader in Translational Cancer Pharmacology, at the National Institute for Cellular Biotechnology in Dublin City University (DCU).
“Translational research is at the interface of clinical and laboratory science. It focuses on developing new and safer medicines and diagnostic tools. We know clinically and scientifically that cancer is a very complex set of diseases. It’s not a specific disease; each cancer is individual to each patient. While some breast cancers, for example, respond very well to treatment in some women, other breast cancers don’t, even if the cancer is at the same stage and looks identical in other ways.
“This is where translational medicine is helping us to better individualise treatment, it’s helping to identify the molecular characteristics that give us the most information about that form of cancer, what is likely to happen to it and what treatments will be most effective.”
This is a two-way process with scientists and clinicians using advanced laboratory techniques to gather basic information on the important fundamental mechanisms underlying cancer and governing growth; progression and treatment response using cultured cell models, clinical samples from patients, and observing differences between normal and disease states, expression of disease biomarkers and response to therapy.
Such work is only meaningful when conducted in partnership with specialist clinical resources, which treat patients in a carefully controlled manner using international standards of treatment and research to collect clinical, diagnostic information and provide high quality patient samples.
One of the labs at the National Institute for Cellular Biotechnology, DCU
This direct collaboration between clinical staff and lab researchers promotes the discovery of disease biomarkers and drug targets that is resulting in more rational drug design, and more effective and safe treatments that can be quickly and efficiently introduced into medical practice via clinical trials.
“It’s taking laboratory research directly to patients. Where putative markers have been identified, you then want to see if it is a valid marker in ‘real’ cancer because, as scientists, we can develop a nice hypothesis in the lab but cancer, in reality, is a lot more complex in the patient,” says Dr O’Connor.
This approach to coordinated translational research has led Irish researchers identifying important new diagnostic markers such as the proteins urokinase plasminogen activator and plasminogen activator inhibitor 1, whose significance in breast cancer treatment was first identified by Professor Joe Duffy, St Vincent’s University Hospital Dublin.

Focusing on emerging anti-cancer drugs
“Until about ten years ago any investigation of a new drug would have gone through a standard development process. A new drug for breast cancer would have gone into a clinical trial of breast cancer patients; the trial would run its course over months or years and after an evaluation was conducted, the researchers would report on the response rate in the whole patient population.
“Nowadays, translational medicine is allowing us to take a closer look at the individual tumours within those breast cancer patients. We can look at additional information to see if there is more we can learn about the treatment, for example, can we identify markers that will tell us which patient will respond or which patients will not? And can we find markers that will tell us early on that the patient has responded to treatment?
“This is very important because many of our tools in clinical cancer research only give information on treatment response several months after treatment begins. This is extremely valuable time as, in some advanced malignancies, it is all too common for the first type of treatment given to have limited effect and therefore patients may be exposed to side effects and toxicity while the agent itself is not helping shrink their tumour and this may only become evident months later. Translational research is providing tools that indicate upfront which patients should or should not receive particular treatments and more rapidly identifying those responding to treatment - and should therefore continue - from those nor responding and should therefore move to another treatment option.
“So translational medicine tries to identify new targets for treatment, new markers that will indicate whether treatment is working or not, and new ways of conducting trials,” he explains.

Biological markers
Biomarkers are molecular characteristics of precancerous or cancerous cells that can aid in predicting cancer development, behaviour, and prognosis. Biomarkers can be grouped into three major categories: diagnostic, prognostic, and predictive.
Diagnostic markers aid in diagnosing disease, such as measurement of the rate of change of PSA levels in prostate cancer or CA-125 in ovarian cancer. Prognostic markers, such as hormone receptors, angiogenic markers, growth factor receptors and proliferation markers, provide information about the likely clinical course of a disease. Predictive markers can help anticipate the course of a disease and how a patient may respond to particular types of therapy. Together with diagnostic and prognostic markers, predictive markers can help physicians formulate a more individualised treatment plan.
“Our clinical trials are moving now away from being focused purely on the anatomical type of cancer that a patient has, whether its breast or brain cancer, for example, to examining the cancer’s molecular characterisation,” says Dr O’Connor.
“It is an evolving area. In a lot of cases now we are starting to get a handle on some of those indicators. We are making discoveries now that may provide us with the tools in the not-too-distant-future to molecularly characterise a person’s cancer and identify the best possible treatment for that particular patient.”
An illustrative case is the identification in 1987 of the human epidermal growth factor receptor 2 (HER2) gene, which is present in about 20% of cases of invasive breast cancer.
Interestingly, the team which identified this protein is led by Professor Denis Slamon, at the UCLA Department of Medicine, who has since been collaborating closely with a number of Irish cancer research institutions to further research on breast cancer.
HER2 is part of a family of genes that play roles in regulating cell growth. Women whose breast cancer had more copies of the HER2 gene spread the fastest and had a worse prognosis.
“When it was originally discovered HER2 was a negative prognostic marker. If your breast cancer demonstrated the over expression of this marker there was a likely to be a poor outcome due to rapid growth of that tumour. But using translational research methods, treatments were developed specifically to target and inhibit the HER2 protein,” Dr O’Connor says. “In some cases it appears that this has given rise to cure, but in the majority of cases what it means is that patients can be given a much less toxic treatment over a long duration that will basically manage and control their breast cancer much more effectively.”
In another exciting development, progress has been made in a treating a particular subtype of lung cancer. In approximately 3 to 5% of Non Small Cell Lung Cancers NSCLC - the most common form of lung cancer - a gene called ALK-1 is found to have fused with another (EML4) and the product drives the growth of this tumour.
In these patients, a recent study found that 90% responded to treatment with a new ALK-targeting drug called Crizotinib. This response is all the more noteworthy as NSCLC generally responds very poorly to standard forms of treatment.
This initial success with Crizotinib is a good illustration of the ultimate goal for translational research; to marry the identification of specific tests, which characterise individual cancers with the novel agents and therapeutic strategies that will achieve high efficacy with minimal toxicity in that specific molecular form of cancer.

Building bridges to the medicine of tomorrow
Examples of other such successes are emerging with increasing regularity in other forms of cancer. This revolution in biotechnology and interdisciplinary collaboration has become critically important in adding to the armamentarium of anti-cancer therapies. Its potential is reflected in the fact that most of the clinical trials in Ireland run by ICORG have a translational component.
National Institute for Cellular Biotechnology, DCU
“Advances in this field can be a frustratingly slow sometimes for patients, their families and researchers. But conducing this research to the highest possible standards is essential, and this takes time,” Dr O’Connor notes. “In the lab we can get results relatively quickly, but clinical research often takes quite a bit longer, because of the complexities of cancer in patients and the vital safeguards that must be employed. It is very satisfying, however, for any researcher to see a hypothesis that developed in the lab, be taken to patients in Irish hospitals in a clinical trial and for any positive result to be found.
“On the negative side, very few people actually understand what translational medicine is and its unique importance in this field. It is only in the last two years that we have started to see funding agencies begin to specifically support this kind of research. The funding environment and the support structures in the hospitals and industry are also still in their infancy.”
Yet, translational research in recent years has yielded not only significant advances in cancer therapeutics but also improvements in the ability of doctors to predict the clinical course of a patient's disease based on individual tumour characteristics.
This collaboration of scientists and doctors, companies and patients, is vital in translating laboratory findings into clinically applicable therapies.
“Translational medicine is always a team approach; it’s never one individual,” stresses Dr O’Connor. “You can have a charismatic leader or advocate, vital for maintaining the momentum but in reality it’s always a team approach. Having good integration between the research nurses, the medical staff, the scientists, the regulatory authorities and pharmaceutical companies, that’s where we are really making advances in Ireland. We’re coming together as a group, a co-operative, and that allows us to do things in an exciting way that we just couldn’t do on our own.”

USEFUL Web links:

All Ireland Cooperative Research Group

The National Institute for Cellular Biotechnology

Molecular Medicine Ireland

Translational research pioneer Professor Dennis Slamon

Further information on Crizotinib

HRB-SFI Translational Research Awards

Oncotype Dx breast cancer test