“For the first time, we are able to completely synthesize anthocyanins in a biological system,” said said Mattheos Koffas, a professor of chemical and biological engineering at Rensselaer, and member of the Center for Biotechnology and Interdisciplinary Studies. “We feed the bacteria glucose and they do the rest. This demonstrates that an inexpensive technology can produce these valuable compounds.”
2017年6月29日 星期四
2017年6月24日 星期六
Biology The curse of the people who never feel pain
http://www.bbc.com/future/story/20170426-the-people-who-never-feel-any-pain
Biology The curse of the people who never feel pain
By David Cox
27 April 2017
At the Institute of Human Genetics in Aachen, Germany, Dr Ingo Kurth is preparing for a rather unusual appointment. She’s collecting blood samples from Stefan Betz, a 21-year-old university student who suffers from a genetic disorder so rare that only a few hundred people worldwide are estimated to have it.
Betz has congenital insensitivity to pain, or CIP. It means he can place his hand in boiling water or undergo an operation without anaesthetic, and yet feel no discomfort whatsoever. In every other way, his sensory perceptions are normal. He sweats when a room is too hot, and shudders at the biting chill of a cold wind. But like almost all who suffer from CIP, Betz finds his condition a curse rather than a blessing.
People with CIP would love to know what pain means and what it feels like to be in pain
“People assume that feeling no pain is this incredible thing and it almost makes you superhuman,” Betz says. “For people with CIP it’s the exact opposite. We would love to know what pain means and what it feels like to be in pain. Without it, your life is full of challenges.”
As a young child, Betz’s parents initially believed he was mildly mentally retarded. “We couldn’t understand why he was so clumsy,” his father Dominic remembers. “He was constantly bumping into things and getting all these bruises and cuts.”
Neither his parents or siblings have the condition, but the diagnosis of CIP eventually came when aged five, he bit off the tip of his tongue, without any apparent pain response. Shortly afterwards he fractured the right metatarsal in his foot, after jumping down a flight of stairs.
From an evolutionary perspective, one of the reasons scientists believe CIP is so rare is because so few individuals with the disorder reach adulthood. “We fear pain, but in developmental terms from being a child to being a young adult, pain is incredibly important to the process of learning how to modulate your physical activity without doing damage to your bodies, and in determining how much risk you take,” Kurth explains.
Without the body’s natural warning mechanism, many with CIP exhibit self-destructive behaviour as children or young adults. Kurth tells the story of a young Pakistani boy who came to the attention of scientists through his reputation in his community as a street performer who walked on hot coals, and stuck knives in his arms without displaying any signs of pain. He later died in his early teens, after jumping from the roof of a house.
So many of the males have killed themselves by their late 20s by doing ridiculously dangerous things, not restrained by pain – Geoff Woods
“Of the CIP patients I’ve worked with in the UK, so many of the males have killed themselves by their late 20s by doing ridiculously dangerous things, not restrained by pain,” says Geoff Woods, who researches pain at the Cambridge Institute for Medical Research. “Or they have such damaged joints that they are wheelchair-bound and end up committing suicide because they have no quality of life.”
Betz has been to hospital more times than he can remember. He has a slight limp in his left leg, due to an infection, known as osteomyelitis, following a tibial bone fracture sustained skateboarding. “You learn that you have to pretend you have pain to prevent yourself from being reckless,” he says. “Which isn’t easy when you don’t know what it is. I now to try to be vigilant otherwise one day my body will just give out.”
But the very mechanisms which cause Betz’s disorder, could one day soon improve the lives of millions globally.
CIP was first reported in 1932 by a New York physician called George Dearborn who described the case of a 54-year-old ticket salesman who claimed not to recall any pain despite a range of experiences such as being impaled by a lathing hatchet as a child, and subsequently running home.
Over the next 70 years, scientists took little notice of this obscure condition which occasionally popped up in the case notes of medical journals around the world. But with the advance of social media making it easier than ever to find groups of people with CIP, scientists began to realise that studying this rare disorder may provide new understanding of pain itself, and how to switch it off for the many afflicted by chronic pain conditions.
The underlying incentive is financial. Pain is a global industry on an almost staggering scale. The world’s population consumes around 14 billion doses of pain-relief medication daily, with estimates suggesting that one in 10 adults are diagnosed with chronic pain each year, lasting for an average of seven years at a time. The reason we feel pain is due to the actions of proteins which live on the surface of our pain neurons, cells which stretch from the skin all the way to the spinal cord. There are six types of pain neuron in total, and when activated by stimuli as varied as high temperatures to the acid in a lemon, they send a signal to the spinal cord where it reaches the central nervous system and is perceived as pain. The brain can shut down this pain signalling network itself if it chooses, through natural chemicals called endorphins produced in situations of high stress or adrenaline.
The world of painkillers is dominated by opiates such as morphine, heroin and tramadol, which work in a similar way to endorphins, including the addictive ‘high’. The consequences have been devastating. In the US, 91 people die every day from opioid overdoses, to the tune of more than half-a-million since the year 2000. Alternatives such as aspirin aren’t effective with severe pain and can cause severe gastrointestinal side-effects over a long period of time. But while the need for breakthroughs in pain research has been desperate, little has been achieved. Until recently, that is.
The company began scouring the globe for similar cases, to try and sequence their DNA
In the early 2000s, a small Canadian biotech company called Xenon Pharmaceuticals heard about a family from Newfoundland where several members of the family were affected by CIP. “The boys in the family had often broken their legs and one even stood on a nail without any apparent sense of pain,” says Simon Pimstone, president and CEO of Xenon.
The company began scouring the globe for similar cases, to try and sequence their DNA. The resulting study found a common mutation in a gene called SCNP9A, which regulates a pathway in the body called the Nav1.7 sodium channel. The mutation knocked out this channel, and with it, the ability to feel pain.
It was the breakthrough the pharmaceutical industry had been waiting for.
“Drugs which inhibit the Nav1.7 channel could be a new way of treating chronic syndromes such as inflammatory pain, neuropathic pain, lower back pain and osteoarthritis,” says Robin Sherrington, senior vice-president of business and corporate development at Xenon, who was heavily involved in the initial study. “And because all sensory functions remain normal in CIP patients apart from the lack of pain, it offers the prospect of minimal side effects.”
Over the past decade, Nav1.7 has sparked a “pain race” across the biotech industry between pharmaceutical giants including Merck, Amgen, Lilly, Vertex and Biogen, all vying to become the first to bring an entirely new class of painkiller to market.
But developing sodium channel blockers which act specifically on the peripheral nervous system, isn’t entirely straightforward, and while the promise is there, it may take another five years to fully know whether inhibiting Nav1.7 is really the key to modulating pain signalling in humans. Xenon themselves are banking that it is. They currently have three products in clinical trials in partnership with Teva and Genentech, one in phase two trials for shingles pain, and two more in the first phase of safety studies.
“Nav1.7 is a difficult and challenging drug target as it’s one of nine sodium channels which are all very similar,” Sherrington says. “And these channels are active in the brain, the heart, the nervous system. So you have to design something which only hits that one particular channel and only works on the tissues you want it to work in. It requires a lot of caution.”
For CIP sufferers themselves, the prospect of a future life with pain and all its advantages remains slim
In the meantime, new pathways behind pain continue to emerge from studying CIP. One of the most exciting is a gene called PRDM12 which appears to work as a master switch, turning on and off a series of genes relating to pain neurons.
“It could be that in chronic pain states, your PRDM12 isn’t working properly and it’s overactive,” Woods says. “If we could rewire that, you could potentially switch the pain neurons back to a normal acquiescent state. The other interesting thing about PRDM12 is that it’s only expressed in pain neurons, so if you had a drug which modulated it you might have an analgesic with very few side effects as it wouldn’t affect any other cells in the body.”
But while the world of painkiller research is benefiting from the uniqueness of those with this extraordinary disorder, for CIP sufferers themselves, the prospect of a future life with pain and all its advantages remains slim.
Pimstone points out that by taking part in studies, these individuals are seen by medical professionals, and in many cases for the first time, begin to receive specialist advice. “Without their contributions we wouldn’t be able to move the field forward in the way we can, so we’re enormously grateful,” he says. “And being part of the medical system benefits them as strategies can be implemented within these families so that kids with this disorder do less harm to themselves growing up. Through these studies, a diagnostic could also become available which can detect CIP early on.”
Gene therapy is not yet at a stage where scientists could contemplate restoring a missing channel and perhaps giving back pain to someone who’s never had it, and for such a small percentage of individuals the financial motives of finding a way simply aren’t there.
But Betz says he lives in hope. “I want to contribute and be able to help the world understand more about pain. Perhaps one day they could use the understanding we gave them, to help us too.”
2017年6月23日 星期五
chimpanzees.在觀察員中會改變習慣 (覓猴等)； Splish splashing spinning gorilla
BBC Science News
Splish splashing spinning gorilla http://bbc.in/2t2b99Y
Splish splashing spinning gorilla http://bbc.in/2t2b99Y
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BBC的GMT節目： chimpanzees.在觀察員中會改變習慣 (覓猴等)
Andrew Whiten - University of St Andrews
https://www.st-andrews.ac.uk › Research portal › Researchers › Andrew Whiten
To elucidate the evolution of these phenomena I study and compare human and non-human primates, especially our closest living relatives, chimpanzees.Chimps pass on knowledge to the next generation - University of St ...
https://www.st-andrews.ac.uk/news/archive/2017/title,1338875,en.php
Jun 1, 2017 - Now, new behavioural experiments with chimpanzees, led by the University of St Andrews, suggests that these apes may indeed share some of ...2017年6月22日 星期四
The 3D printer, an invention by Charles Hull.of the 1980s that triumphs 30 years later
It was a night back in 1983 when this engineer woke up his wife to show her his new achievement: he managed to print a black plastic cup with a new technique he invented himself and that he called stereolithography. This is the amazing story of Charles Hull. (Partner content via BBVA OpenMind)
2017年6月21日 星期三
The women scientists who took India into space
"We are still carrying cultural loads on our backs and many women think their priorities lie elsewhere, at home." (via BBC India)
2017年6月14日 星期三
在日本學術界的傳統上，著書、譯書是奠定科學基礎的重要工作。--撰文／高涌泉
「朝永的書竟然是小柴所譯這件事，可能會令一些人感到意外，因為一來寫書或翻譯書一般是理論學家的工作，二來翻譯並不被認為是「有助於自身科學事業」的事。不過日本學術界傳統上似乎並不看輕翻譯這回事」
大師譯大師
- 在日本學術界的傳統上，著書、譯書是奠定科學基礎的重要工作。
Fight Against Cancer with Artificial Intelligence and Big Data
When MIT professor Regina Barzilay was diagnosed with breast cancer, her life and research were turned upside down. In the endless shuffling between hospitals, she realized that most of the information being recorded about patients was not being used. This is how Big Data and AI can help fighting cancer.
2017年6月11日 星期日
This baby bird, trapped in amber, lived alongside the dinosaurs
A baby bird, encased in amber, is giving researchers an unprecedented glimpse 100 million years into the past:
A radical new hypothesis in medicine: give patients drugs they know don’t work. You Can Have the Placebo Effect, Even If You Know It's a Placebo
Oxford University Scientific Society
2010.12.25
待討論
Read original story in PLoS | Thursday, Dec. 23, 2010
Meet the Ethical Placebo: A Story that Heals
Irving Kirsch at the University of Hull, photo by Bo Tenberg
The word placebo is ancient, coming to us from the Latin for “I shall please.” As far back as the 14th Century, the term already had connotations of fakery, sleaze, and deception. For well-to-do Catholic families in Geoffrey Chaucer’s day, the custom at funerals was to offer a feast to the congregation after the mourners sang the Office for the Dead (which contains the phrase placebo Domino in regione vivorum, “I shall please the Lord in the land of the living”). The unintended effect of this largesse was to inspire distant relatives and former acquaintances of the departed to crawl out of the woodwork, weeping copiously while praising the deceased, then hastening to the buffet. By the time Chaucer wrote his Canterbury Tales, these macabre freeloaders had been christened “placebo singers.”
In modern medicine, placebos are associated with another form of deception — a kind that has long been thought essential for conducting randomized clinical trials of new drugs, the statistical rock upon which the global pharmaceutical industry was built. One group of volunteers in an RCT gets the novel medication; another group (the “control” group) gets pills or capsules that look identical to the allegedly active drug, but contain only an inert substance like milk sugar. These faux drugs are called placebos.
Inevitably, the health of some people in both groups improves, while the health of others grows worse. Symptoms of illness fluctuate for all sorts of reasons, including regression to the mean. Since the goal of an RCT, from Big Pharma’s perspective, is to demonstrate the effectiveness of a new drug, the return to robust health of a volunteer in the control group is considered a statistical distraction. If too many people in the trial get better after downing sugar pills, the real drug will look worse by comparison — sometimes fatally so for the purpose of earning approval from the Food and Drug Adminstration.
For a complex and somewhat mysterious set of reasons, it is becoming increasingly difficult for experimental drugs to prove their superiority to sugar pills in RCTs, which was the subject of an in-depth article I published in Wired called “The Placebo Problem,” recipient of this year’s Kavli/AAAS Science Journalism of the Year award for a magazine feature.
Only in recent years, however, has it become obvious that the abatement of symptoms in control-group volunteers — the so-called placebo effect — is worthy of study outside the context of drug trials, and is in fact profoundly good news to anyone but investors in Pfizer, Roche, and GlaxoSmithKline. The emerging field of placebo research has revealed that the body’s repertoire of resilience contains a powerful self-healing network that can help reduce pain and inflammation, lower the production of stress chemicals like cortisol, and even tame high blood pressure and the tremors of Parkinson’s disease.
Jumpstarting this network requires nothing more or less than a belief that one is receiving effective treatment — in the form of a pill, a capsule, talk therapy, injection, IV, or acupuncture needle. The activation of this self-healing network is what we really mean when we talk about the placebo effect. Though inert in themselves, placebos act as passwords between the domain of the mind and the domain of the body, enabling the expectation of healing to be translated into cascades of neurotransmitters and altered patterns of brain activity that engender health.
That’s all well and good, but what does it mean in the real world of people getting sick? You can hardly expect the American Medical Association to issue a wink and a nod to doctors, encouraging them to prescribe sugar pills for seriously disabling conditions like chronic depression and Parkinson’s disease. Meanwhile, more and more studies each year — by researchers like Fabrizio Benedetti at the University of Turin, author of a superb new book called The Patient’s Brain, and neuroscientist Tor Wager at the University of Colorado — demonstrate that the placebo effect might be potentially useful in treating a wide range of ills. Then why aren’t doctors supposed to use it?
The medical establishment’s ethical problem with placebo treatment boils down to the notion that for fake drugs to be effective, doctors must lie to their patients. It has been widely assumed that if a patient discovers that he or she is taking a placebo, the mind/body password will no longer unlock the network, and the magic pills will cease to do their job.
Now, however, a group of leading placebo researchers — including Irving Kirsch at the University of Hull in England (who I interview at length below) and Ted Kaptchuk at Harvard — has produced a little bombshell of a study that makes these assumptions obsolete. For “Placebos Without Deception,” the researchers tracked the health of 80 volunteers with irritable bowel syndrome for three weeks as half of them took placebos and the other half didn’t. A painful, chronic gastrointestinal condition, IBS is serious business. It’s one of the top ten reasons why people seek medical care worldwide, accounting for millions of dollars a year in health care expenditures and lost work-hours.
In a previous study published in the British Medical Journal in 2008, Kaptchuk and Kirsch demonstrated that placebo treatment can be highly effective for alleviating the symptoms of IBS. This time, however, instead of the trial being “blinded,” it was “open.” That is, the volunteers in the placebo group knew that they were getting only inert pills — which they were instructed to take religiously, twice a day. They were also informed that, just as Ivan Pavlov trained his dogs to drool at the sound of a bell, the body could be trained to activate its own built-in healing network by the act of swallowing a pill.
In other words, in addition to the bogus medication, the volunteers were given a true story — the story of the placebo effect. They also received the care and attention of clinicians, which have been found in many other studies to be crucial for eliciting placebo effects. The combination of the story and a supportive clinical environment were enough to prevail over the knowledge that there was really nothing in the pills. People in the placebo arm of the trial got better — clinically, measurably, significantly better — on standard scales of symptom severity and overall quality of life. In fact, the volunteers in the placebo group experienced improvement comparable to patients taking a drug called alosetron, the standard of care for IBS.
Meet the ethical placebo: a powerfully effective faux medication that meets all the standards of informed consent.
The study is hardly the last word on the subject, but more like one of the first. Its modest sample size and brief duration leave plenty of room for followup research. (What if “ethical” placebos wear off more quickly than deceptive ones? Does the fact that most of the volunteers in this study were women have any bearing on the outcome? Were any of the volunteers skeptical that the placebo effect is real, and did that affect their response to treatment?) Before some eager editor out there composes a tweet-baiting headline suggesting that placebos are about to drive Big Pharma out of business, he or she should appreciate the fact that the advent of AMA-approved placebo treatments would open numerous cans of fascinatingly tangled worms. For example, since the precise nature of placebo effects is shaped largely by patients’ expectations, would the advertised potency and side effects of theoretical products like Placebex and Therastim be subject to change by Internet rumors, requiring perpetual updating?
100% pure placebo
We’re also discovering that the power of narrative is embedded deeply in our physiology. Perhaps that’s not surprising. In the long centuries before doctors discovered antibiotics, they often had little else but an observant eye, a listening ear, and a bag of nostrums with names like decoction of barley and compound infusion of roses to offer their desperately ill patients.
In an age of computerized diagnostics, talking about the power of storytelling in health care seems like a throwback to those medical Dark Ages. After reading the new study, however, one of the pioneers of placebo research, anthropologist Dan Moerman at the University of Michigan, noted how much even the volunteers who didn’t get placebos benefited from the support and attention of clinicians.
“I was really surprised at how well the non-placebo group did,” Moerman says in email. “Note I don’t call them a ‘no treatment group’ because they, and everyone else, received exemplary treatment here: they were listened to, examined, encouraged, supported. They were able to talk with, and be taken seriously by, people who understood their issues, things they probably had serious difficulty discussing with their own families. I think it likely that the effectiveness of the placebos above and beyond all the other treatment would have been diminished without the whole system of compassionate care.”
At the same time, as Kirsch explains in our interview, the volunteers who took placebos felt significantly better than those who didn’t. The act of taking the pills made a difference.
Placebo expert Amir Raz at McGill University observes that the new study follows up on a groundbreaking experiment conducted in 1964 by Lee Park and Uno Covi, who administered “open” placebos to 15 patients from a psychiatric clinic and tracked similar levels of improvement in their anxiety. In a paper slated to be published in the April 2011 issue of the Canadian Journal of Psychiatry, Raz will talk to many physicians who doubt that one has to lie to patients for placebos to be effective. In fact, in the real world of doctoring, many physicians prescribe medications at dosages too low to have an effect on their own, hoping to tap into the body’s own healing resources — though this is mostly acknowledged only in whispers, as a kind of trade secret.
Kirsch’s 2010 book The Emperor’s New Drugs caused a huge stir by claiming that the effectiveness of antidepressants — one of the top-selling classes of drugs in the world — may be entirely dependent on the placebo effect. Before spending time with him at a placebo workshop hosted at McGill in July, I was frankly expecting to meet a fiery anti-pharma avenger – albeit one with a compelling argument backed up by data.
Instead, Kirsch is a soft-spoken, modest, diligent, boyishly handsome 67-year-old psychologist who thoroughly understands why his notions are so upsetting to people who insist that their lives have been turned around by Paxil or Lexapro. He also has an intriguing personal history that includes organizing against the Vietnam War with Bertrand Russell, producing a Grammy-nominated comedy album in 1973 with the editors of National Lampoon, and playing violin in the Toledo Symphony behind Aretha Franklin. Kirsch is currently working on a new book about the potential of placebo therapy.
Silberman: What’s the most subversive aspect of this new study?
Kirsch: Simply that placebos work even when you tell people that they’re placebos. To me that’s fascinating. As is the fact that patients can experience substantial and clinically meaningful improvement of the symptoms of irritable bowel syndrome when given placebos.
One of the assumptions that we made in this study, however, is that you have to offer the patients a convincing rationale to use placebos as well as giving them a pill. That’s the next thing we have to test.
Silberman: What kinds of ailments are amenable to placebo treatment?
Kirsch: Depression, anxiety disorders, and pain; pain in particular is highly responsive to placebo therapy. Irritable bowel syndrome — we’ve shown that not only in this study, but in one published in the British Medical Journal a couple of years ago. Parkinson’s Disease, ulcers, and asthma too. There’s a long list of conditions treatable with placebos that have some subjective component and can be intensified by conditions like stress.
Silberman: If all of these ailments have a subjective component, does that mean they share a set of neurological mechanisms?
Kirsch: I’m afraid that’s outside my area of expertise. But I know what these conditions don’t share in common. The kinds of effects you see in the brain when people respond to a placebo depends on the condition you’re supposed to be treating. So if you take a placebo analgesic, you get reductions in activity in the brain’s pain matrix. If you take a placebo antidepressant, you get changes in brain activity in areas related to depression.
Silberman: Does the placebo response tell us anything about how active medicines work?
Kirsch: For any condition susceptible to placebos, the placebo effect is a component of the response to active medication. In most cases, placebo effects and drug effects are additive — the net response to the medication is larger because of placebo effects than it would be on its own.
Silberman: You’ve done a lot of work analyzing placebo effects in antidepressant therapy, which you write about in your book The Emperor’s New Drugs. Has your opinion of antidepressants evolved at all?
Kirsch: The more I learn, the more convinced I become that the benefits of drugs for depression are not biologically driven, but driven by the placebo effect. The thing that convinces me most is that nearly all drugs for depression — despite having very different chemical compositions — are of equal benefit. In other words, you have drugs that are completely different in what they do chemically — even drugs that operate by opposing mechanisms — creating the same level of effect.
The most commonly employed antidepressants are supposed to increase the amount of serotonin in synapses in the brain, but there are also antidepressants that decrease the level of serotonin in the brain, and they both have the same effect therapeutically. The effects of these drugs seem to be completely independent of their chemical composition.
Silberman: Dan Moerman mentioned to me in an email that he was surprised by how well the non-placebo group did in your study.
Kirsch: That’s true. We said that we compared open label placebo to a no-treatment control group, but actually, the ”no-treatment” description is not entirely accurate in this case. The patients in the control group met with the clinician before being given the pills and midway between the beginning and end of the study. Both visits were in the context of a warm, supportive, patient-practitioner relationship. Like many other researchers, we assume that the therapeutic relationship is an important component of the placebo effect.
But many people — including doctors — think that the therapeutic relationship entirely accounts for the placebo effect. Our data show that this is not true. If the placebo effect was entirely due to the therapeutic relationship — the time, attention, warmth, and enthusiasm communicated by the doctor — then our placebo pill would not have produced any effect beyond that seen in our “no-treatment” control condition, because the no-treatment control patients received the same level of therapeutic relationship as that received by patients in the placebo pill condition. That tells us two things –one, that giving patients the placebo pill improved their condition, and two, that the difference in improvement was due to getting the pill. It was not due to the therapeutic relationship.
Silberman: One of the ways that you prepped the volunteers in this trial was that you informed them that placebo effects work via conditioning, like Pavlov’s dogs being trained to salivate at the sound of a bell. What trains people all over the world to respond to act of taking a pill?
Kirsch: The existence of successful treatments. People come to expect and believe that they’re going to get better if they take medication. The whole process of going to a physician and being treated reinforces this belief. That constitutes the basic aspects of classical conditioning. Eventually, the pill alone is enough to produce a placebo effect, whether it contains an active drug or not.
Silberman: Does direct-to-consumer advertising also play a role? In America, when you open a magazine, the good-looking jock playing with puppies in the sun is the formerly depressed patient on Zoloft.
Advertisement for Abilify, used to treat depression, schizophrenia, bipolar disorder, and autism-related irritability
Silberman: What would a world in which placebos were given openly by doctors look like?
Kirsch: Our study points to something that a number of people have suspected, but has been hard to demonstrate under controlled conditions: We have the capacity for healing physical conditions through psychological means. First, we have to accept that. Studies of placebo effects are great demonstrations of it.
You might think of this healing capacity as a self-regulatory mechanism. Then the question then becomes how best to unlock it. This kind of research shows the potential of our being able to treat certain conditions without drugs — particularly in cases where we don’t have effective drugs, and/or where the drugs we have are not much more effective than what we can accomplish with placebos. And especially in cases where the drugs carry serious risks.
Silberman: A lot of very smart people dismiss homeopathy, acupuncture, and other alternate treatments as nothing more than quackery for dullards — “woo,” as P.Z. Myers or Ben Goldacre might put it. But couldn’t the placebo response play the role of being, in a sense, the “active principle” of woo? For example, I recently saw a controlled trial of homeopathic therapy for rheumatoid arthritis that concluded that the effectiveness of the therapy was due to the homeopathic consultation process, not the little pills themselves. Your colleague Ted Kaptchuk spoke to me for my Wired article about the importance of “therapeutic ritual” in eliciting the placebo response, and homeopathic consultation — even if the notion that pills containing a few molecules at most of an active ingredient seems obviously ridiculous — is a good example of an elaborate therapeutic ritual. I think the door is still open on whether acupuncture does more than jump-start the placebo response…
Traditional map of 经络, the acupuncture meridians
We know from our research the things that make a difference: how much time you spend with a patient, how supportive and empathic you are, how well you listen, and how confident you are in being able to help. Complimentary and alternative medicine practitioners are particularly good at these things. These are obviously things that physicians can do as well, and some are very good at eliciting placebo effects.
But those qualities are becoming more rare in conventional medical practice. Certainly here in the UK, it’s very uncommon to have a good placebo intervention in primary care, because the standard visit with the doctor is ten minutes at most.
Silberman: Ten minutes sounds long to me. If I see my doctor for three minutes as she rushes around, it’s a good day.
Kirsch: In the IBS study we did in 2008, we maximized the amount of time spent in the initial interview, and other qualities of listening and empathy, and got much more substantial placebo effects.
Silberman: These days, however, the emphasis is increasingly on data-driven medicine — blood tests, genome and proteome scans, and the search for biomarkers. Studies like this suggest that narrative medicine as it was practiced in the 19th century — the doctor listening to the patient, hearing the story of the symptoms, and reframing it as a story of how the patient will get better — also plays a crucial role in healing.
Kirsch: We’re breaking the boundary between the two approaches. The reason we do studies like this is to make placebo research data-driven. We’re starting to build up a database on the effects of enhancing patient-physician contact, and on the administration of placebos openly and honestly, without deception.
Silberman: Have you had any hostile responses to your book from people who worry that by telling depressed people that antidepressants are really placebos, the pills will stop working?
Photo of Irving Kirsch by Bo Tenberg
Silberman: Has your research changed the way you think about taking medicine?
Kirsch: Interesting question. It has made me more wary. It certainly makes me less likely to talk to my doctor about getting an antidepressant if I’m feeling down or sad.
Silberman: What kinds of follow-up studies are needed now?
Kirsch: We know that open placebo treatment works for IBS. Does it also work for depression? How crucial is telling patients about the placebo effect? Might placebo therapy work even without giving patients a convincing rationale? My guess would be that it wouldn’t, but I don’t really know for sure.
Silberman: One interesting aspect of this study is that it suggests that are two layers of belief in the brain — one that knows there’s nothing in this pill, and another that knows that a placebo can be an effective treatment. It’s as if the brain can entertain two different notions of the effectiveness of a pill at once.
Kirsch: Yes, but they’re not contradictory notions. I believe in both. I know that this pill does not contain a physically active ingredient, and I also understand the conditioning process. I know that the placebo effect is real, so I understand that this inert pill might help trigger that healing response within me. We need to recognize and understand that patients are active agents in their treatment, not passive. The placebo effect does not come from the pill. It comes from the patient.
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