Only From a Pre-Med

fuckyeahmedicalstuff: Open heart surgery in Modares hospital;...

hooptyhooptyhoopdehoop — Mon, 25 Mar 2013 10:41:23 -0400

fuckyeahmedicalstuff:

Open heart surgery in Modares hospital; Tehran, Iran.

Photo

hooptyhooptyhoopdehoop — Thu, 14 Feb 2013 18:40:53 -0500

neurosciencestuff: Some Autism Behaviors Linked to Altered...

hooptyhooptyhoopdehoop — Thu, 14 Feb 2013 18:14:12 -0500

neurosciencestuff:

Some Autism Behaviors Linked to Altered Gene

Scientists at Washington University School of Medicine in St. Louis have identified a genetic mutation that may underlie common behaviors seen in some people with autism, such as difficulty communicating and resistance to change.

An error in the gene, CELF6, leads to disturbances in serotonin, a chemical that relays messages in the brain and has long been suspected to be involved in autism.

The researchers identified the error in a child with autism and then, working in mice, showed that the same genetic alteration results in autism-related behaviors and a sharp drop in the level of serotonin circulating in the brain.

While the newly discovered mutation appears to be rare, it provides some of the first clues to the biological basis of the disease, the scientists report Feb. 13 in the Journal of Neuroscience.

“Genetically, autism looks very complicated, with many different genetic routes that lead to the disease,” says lead author Joseph D. Dougherty, PhD, an assistant professor of genetics at Washington University. “But it’s not possible to design a different drug for every child. The real key is to find the common biological pathways that link these different genetic routes and target those pathways for treatment.”

Autism is known to have a strong genetic component, but the handful of genes implicated in the condition so far explain only a small number of cases or make a small contribution to symptoms.

This led Dougherty and senior author Nathaniel Heintz, PhD, a Howard Hughes Medical Institute investigator at Rockefeller University, to speculate that some of the most common behavioral symptoms of autism may be caused by disruptions in a common biological pathway, like the one involved in serotonin signaling.

neurosciencestuff: Stopping cold: USC scientists turn off the...

hooptyhooptyhoopdehoop — Thu, 14 Feb 2013 18:12:49 -0500

neurosciencestuff:

Stopping cold: USC scientists turn off the ability to feel cold

USC neuroscientists have isolated chills at a cellular level, identifying the sensory network of neurons in the skin that relays the sensation of cold.

David McKemy, associate professor of neurobiology in the USC Dornsife College of Letters, Arts and Sciences, and his team managed to selectively shut off the ability to sense cold in mice while still leaving them able to sense heat and touch.

In prior work, McKemy discovered a link between the experience of cold and a protein known as TRPM8 (pronounced trip-em-ate), which a sensor of cold temperatures in neurons in the skin, as well as a receptor for menthol, the cooling component of mint. Now, in a paper appearing in the Journal of Neuroscience on February 13, McKemy and his co-investigators have isolated and ablated the neurons that express TRPM8, giving them the ability to test the function of these cells specifically.

Using mouse-tracking software program developed by one of McKemy’s students, the researchers tested control mice and mice without TRPM8 neurons on a multi-temperature surface. The surface temperature ranged from 0 degrees to 50 degrees Celsius (32 to 122 degrees Farenheit), and mice were allowed to move freely among the regions.

The researchers found that mice depleted of TRPM8 neurons could not feel cold, but still responded to heat. Control mice tended to stick to an area around 30 degrees Celsius (86 degrees Fahrenheit) and avoided both colder and hotter areas. But mice without TRPM8 neurons avoided only hotter plates and not cold — even when the cold should have been painful or was potentially dangerous.

In tests of grip strength, responses to touch, or coordinated movements, such as balancing onto a rod while it rotated, there was no difference between the control mice and the mice without TRPM8-expressing neurons.

By better understanding the specific ways in which we feel sensations, scientists hope to one day develop better pain treatments without knocking out all ability to feel for suffering patients.

“The problem with pain drugs now is that they typically just reduce inflammation, which is just one potential cause of pain, or they knock out all sensation, which often is not desirable,” McKemy said. “One of our goals is to pave the way for medications that address the pain directly, in a way that does not leave patients completely numb.”

bekindplzrewind: fyeahchemistry: (photo credit) via Rajini...

hooptyhooptyhoopdehoop — Thu, 14 Feb 2013 18:10:43 -0500

bekindplzrewind:

fyeahchemistry:

(photo credit)

via Rajini Rao on Google+, for #ScienceSunday:

‘Smallest rotary motor in biology, the ATP synthase.

All the work done in your body is fueled by breaking a chemical bond in ATP, the “currency of energy”. Did you know that you convert your body weight (or an estimated 50 kg) of ATP per day?!

Where does this ATP come from?

It is synthesized by an incredibly sophisticated molecular machine, the ATP synthase, embedded in the inner membrane of our mitochondria. Energy from the oxidation of food results in protons being pumped across the membrane to create a proton gradient. The protons drive the rotation of a circular ring of proteins in the membrane that in turn move a central shaft. The shaft interacts sequentially with one of 3 catalytic sites within a hexamer, making ATP (little butterflies in the movie!). The ATP synthase rotates about 150 times/second

To visualize the rotation under a microscope, a very long fluorescent rod (actin filament) was chemically attached to the central shaft. Watch real movies (not animations!) of the enzyme spinning here: http://www.k2.phys.waseda.ac.jp/F1movies/F1long.htm

Notice the rotation is slower with longer rods. The rotor produces a torque of 40 pN nm (40 pico Newtons x nanometer), irrespective of the load. This would be the force you would need to rotate a 500 m long rod while standing at the bottom of a large swimming pool at the rate shown in the movie.

How did this amazing rotor evolve?

The hexameric structure is related to DNA helicases that rotate along the DNA double helix, using ATP to unzip the two strands apart. The H+ motor has precedence in flagella motors that use proton gradients to drive rotation of long filaments, allowing bacteria to tumble through their surroundings. At some point, a H+ driven motor came together with a helicase like hexamer to create a rotor driving the hexamer in reverse, to synthesize ATP.

The 1997 Nobel prize in Chemistry was awarded to John Walker and Paul Boyer for solving the structure and cyclical mechanism of the ATP synthase, respectively. This amazing enzyme was also the subject of my own Ph.D. thesis, and my first love!’

For #ScienceSunday curated by +Allison Sekuler and +Robby Bowles

ATP synthase is an amazing little thing. It was, personally, what got me hooked on biochemistry.

LOOK AT THAT. JUST LOOK AT IT GO.

Amazing.

hooptyhooptyhoopdehoop: Latest reading material. Cannot wait...

hooptyhooptyhoopdehoop — Thu, 07 Feb 2013 00:13:53 -0500

hooptyhooptyhoopdehoop:

Latest reading material. Cannot wait for this.

Photo

hooptyhooptyhoopdehoop — Wed, 30 Jan 2013 21:11:39 -0500

neuromorphogenesis: A brain protein called vimentin can...

hooptyhooptyhoopdehoop — Wed, 23 Jan 2013 15:29:00 -0500

neuromorphogenesis:

A brain protein called vimentin can indicate damage to the hippocampus following binge drinking

Binge drinking is known to increase the risk of developing dementia and/or brain damage.

A new study used rodents to test markers of neurodegeneration to determine a threshold for brain damage.

The vimentin brain protein can indicate damage to the hippocampus after 24 hours of binge-like drinking.

Chronic drinking is known to have detrimental health effects such as cardiac and liver problems, cognitive impairments, and brain damage. Binge drinking in particular is known to increase the risk of developing dementia and/or brain damage, yet little is known about an exact threshold for the damaging effects of alcohol. A study using rodents to examine various markers of neurodegeneration has found that brain damage can occur with as little as 24 hours of binge-like alcohol exposure.

Results will be published in the March 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

“We know that the extent of damage following alcohol exposure depends heavily on the manner in which it is consumed,” said Kimberly Nixon, associate professor of pharmaceutical sciences at The University of Kentucky as well as corresponding author for the study. “Human studies suggest that binge-pattern drinking is more closely associated with brain damage. One study, for example, reported that binge drinking at least once per month in adulthood significantly increases the risk of developing dementia later in life. Animal models help provide the critical information that binge drinking, which produces high blood alcohol levels, directly causes damage.”

“The exact threshold for the damaging effects of alcohol on the brain is unclear,” commented Fulton T. Crews, John Andrews Distinguished Professor and director of the Center for Alcohol Studies at the University of North Carolina. “It is likely that the higher the blood alcohol level the greater the damage, however, this manuscript only studies binge drinking, using vimentin and flurojade B as markers of neurotoxicity.”

“People hear from multiple sources that low-moderate alcohol consumption can be beneficial, and then we come along and say that heavy alcohol use leads to detrimental outcomes,” said Nixon. “People then want to know what the line is between beneficial and detrimental Unfortunately, we don’t know exactly. However, our study suggests that it may be even less than previously thought.”

Nixon and her colleagues administered a nutritionally complete liquid diet to adult male Sprague-Dawley rats that additionally contained either alcohol (25% w/v) or isocaloric dextrose every eight hours for either one or two days. The rodents were sacrificed immediately following, two days after, or seven days after alcohol exposure and their brain tissues were examined.

“This was really a simple study that took advantage of some new ‘tools’ to look for evidence of brain damage,” explained Nixon. “In other words, we didn’t look for dying cells themselves, but we looked at more indirect indices of damage by looking at what happens to astroglia, one of the ‘supporting’ cells for neurons. Astroglia react to brain damage by expressing several proteins that they do not normally express under healthy, happy conditions, one of which is an intermediate filament protein called vimentin. We saw a remarkable number of cells expressing this marker It is one of those ‘here is your brain, here is your brain on drugs’ kind of findings where the expression was obvious to the naked eye in many brains with as little as 24 hours of high blood alcohol levels.”

Nixon added that, because rodents metabolize alcohol significantly faster than humans do, it is important to look at the actual concentration of alcohol in the blood in order to translate this to the human condition. “These rats had blood alcohol levels that were more than four times the legal driving limit, which for humans would require excessive drinking in the nature of a 12-pack of beer, a couple bottles of wine, or half of fifth of whisky. Unfortunately, drinking self-reports and blood alcohol level data from emergency rooms confirm that this level of drinking is common in those with alcohol use disorders.”

“Rodent brain damage can model human damage,” noted Crews. “Vimentin seems to be a good marker of glial activation that shows that one day of binge drinking can cause some brain damage that persists and grows after a week of abstinence. However, both rodent and human brain damage generally require long-term alcohol consumption that models alcoholism and not the acute responses studied in this manuscript.”

Nixon agreed. “The lack of overt neuronal deterioration suggests that a single, short-term, high-level binge probably does not result in functional changes and/or cognitive deficits,” she said. “However, since alcoholics experience multiple binges throughout their lifetime, it is important to consider that each successive binge, starting with the very first one, affords some level of damage to the brain. Therefore, theoretically, with multiple binges comes a cumulative detrimental effect where pronounced cognitive, behavioral, and structural effects are observed.”

Nixon said this study demonstrates that new discoveries are always possible. “You have to know where and when to look for some of these effects,” she said. “The reason why this discovery wasn’t made previously is merely due to groups, ourselves included, not taking the time to thoroughly investigate these lower threshold doses with some pretty specific time points. Chasing down a threshold is not a sexy topic and it was actually fairly risky in that it was possible that we would have had all negative effects. Nonetheless, the take-home message of our data is that even one short-duration binge-alcohol experience – which is unfortunately similar to what young adults may experience during spring break or weekend partying - may start a cascade that leads to brain damage.”

Beyond the Oath: A Word With First Year

hooptyhooptyhoopdehoop — Fri, 18 Jan 2013 11:11:03 -0500

Beyond the Oath: A Word With First Year:

aspiringdoctors:

medicalstate:

For the students out there who will soon begin their first year in medical school, let me say congratulations and welcome. There is a long road ahead of you. After reflecting on the experiences I have had and the observations I have made, I have here a list of 16 words of advice to set the course. Here is a quick guide to first year:

Take some time in those first few weeks to build your network. The people in your class are the ones who will be your friends, support, and future colleagues for the next few years. You will need to find people you can count on.

Do not let the white coat or stethoscope fool you. Your friend probably does not have that rare syndrome you just studied and you probably do not have a ruptured triple-A.

Study hard. Get quality studying done and avoid the distractions. Make the most of your study hours so you can…

Find balance. This is your out, a way to get away from medicine and back to your old life. Take some time off for yourself and adjust it accordingly depending on how much you need to study. But always take some time for yourself, your family, friends, and partner. Always.

Sleep when you need. Sleeping hours disappear quickly over time so when you have a day off, get some extra shut eye. Also, if you have to choose between an all-nighter and sleep, go with the sleep.

Caffeine. It is an unavoidable fact of medical school but take it from me, put it off as long as you can. At this point in your career if you can avoid it do so. Would not want to have it lose its edge down the road now would we?

Stay healthy. Stay fit and eat fresh. Part of finding balance is taking the time to keep your body in shape and have a wholesome meal every now and then that needs more than three minutes in a microwave. Your body will thank you and you will feel better.

Practice interviews and clinical skills. I remember when it seemed awkward watching one classmate interview another. Take those moments seriously and learn from them. These are skills you need to carry with you forever now. Practice makes perfect so do a little bit of clinical skills every now and then with your friends and family.

Anatomy labs. Working with cadavers for the first time is intimidating so avoid the hands and face, the two most human elements of a person until you feel comfortable. Also, it can be easy to forget these cadavers were people once, remember to treat them with respect.

Invest in your equipment. Shoes, stethoscopes, white coat, what have you, make sure the parts that last should, and make sure you are comfortable in them.

Save your money when possible. Do you really need that gratuitous Starbucks? Do you need to get the pair of jeans? Medical school is costly and saving anywhere will eventually add up, even if it only puts a small dent in your debt. Seek out free things when possible. Free lunches or food-provided seminars are great for these.

Be careful of what you say, how you say it and where you say it. The world of medicine is wrought with privacy and confidentiality concerns so learn to mind your surroundings before discussing something, especially if it involves a patient, real or not.

Thick skin. Generally the people who work with you are nice but you will need to develop dragon skin. Expectations run high as you go through medical school and you will constantly enter situations where you do not know or make mistakes. Try not to take what people say at you personally.

In the same vein, do not be overly hard on yourself. You are still learning and at this stage of your training there will be mistakes and bad calls. Take them in stride, learn from them, and move on.

Be a moderate learner. Learn what you need to and maybe a bit more out of interest but take solace in knowing that you will not be able to study everything in a year. Stay within reason. Do not be obnoxiously keen. It will end badly.

On a similar note, getting into medical school is not a license to become arrogant or obnoxious. Do not falter here when you have just made it through the door; it is a reputation you do not want following you around. Keep it together.

Good luck and take care.

Related post: A Word With Second Year.
Also check out the lists by wayfaringmd, md-admissions, and cranquis.

I’m reblogging this as both a reminder to myself and as advice to my incoming colleagues.

Samsies! Thanks Medicalstate!

neuroanatomyblog: Comparison of SNS (Somatic Nervous System -...

hooptyhooptyhoopdehoop — Fri, 11 Jan 2013 08:12:37 -0500

neuroanatomyblog:

Comparison of SNS (Somatic Nervous System - Voluntary) to ANS (Autonomic Nervous System - Visceral)

ANS differs from the SNS in:

Thier effectors
SNS innervates skeletal muscle and ANS innervates smooth and cardiac muscle and glands

Efferent pathways
SNS - cell bodies of the motor neuron are in the CNS, and their axons extend in spinal nerves all the way to skeletal muscles

ANS - two neuron chain
The cell body of the first neuron (preganglionic neuron) resides in the brain or spinal cord

Its axon (preganglionic axon) synapses with the second motor neuron (ganglionic neuron) in an autonomic ganglion outside the CNS

The axon of the ganglionic neuron (postganglionic axon) extends to the effector organ

Target organ responses - neurotransmitter effects
SNS - acetylcholine released at their synapse

ANS - norepinephrine, epinephrine and acetylcholine

neuromorphogenesis: Why Do We Blink So Frequently? New research...

hooptyhooptyhoopdehoop — Sun, 06 Jan 2013 12:00:51 -0500

neuromorphogenesis:

Why Do We Blink So Frequently?

New research indicates that the brain enters a momentary state of wakeful rest when we blink, perhaps allowing us to focus better afterward.

We all blink. A lot. The average person blinks some 15-20 times per minute—so frequently that our eyes are closed for roughly 10% of our waking hours overall.

Although some of this blinking has a clear purpose—mostly to lubricate the eyeballs, and occasionally protect them from dust or other debris—scientists say that we blink far more often than necessary for these functions alone. Thus, blinking is physiological riddle. Why do we do it so darn often? In a published paper in the Proceedings of the National Academy of Sciences, a group of scientists from Japan offers up a surprising new answer—that briefly closing our eyes might actually help us to gather our thoughts and focus attention on the world around us.

The researchers came to the hypothesis after noting an interesting fact revealed by previous research on blinking: that the exact moments when we blink aren’t actually random. Although seemingly spontaneous, studies have revealed that people tend to blink at predictable moments. For someone reading, blinking often occurs after each sentence is finished, while for a person listening to a speech, it frequently comes when the speaker pauses between statements. A group of people all watching the same video tend to blink around the same time, too, when action briefly lags.

As a result, the researchers guessed that we might subconsciously use blinks as a sort of mental resting point, to briefly shut off visual stimuli and allow us to focus our attention. To test the idea, they put 10 different volunteers in an fMRI machine and had them watch the TV show “Mr. Bean” (they had used the same show in their previous work on blinking, showing that it came at implicit break points in the video). They then monitored which areas of the brain showed increased or decreased activity when the study participants blinked.

Their analysis showed that when the Bean-watchers blinked, mental activity briefly spiked in areas related to the default network, areas of the brain that operate when the mind is in a state of wakeful rest, rather than focusing on the outside world. Momentary activation of this alternate network, they theorize, could serve as a mental break, allowing for increased attention capacity when the eyes are opened again.

To test whether this mental break was simply a result of the participants’ visual inputs being blocked, rather than a subconscious effort to clear their minds, the researchers also manually inserted “blackouts” into the video at random intervals that lasted roughly as long as a blink. In the fMRI data, though, the brain areas related to the default network weren’t similarly activated. Blinking is something more than temporarily not seeing anything.

It’s far from conclusive, but the research demonstrates that we do enter some sort of altered mental state when we blink—we’re not just doing it to lubricate our eyes. A blink could provide a momentary island of introspective calm in the ocean of visual stimuli that defines our lives.

Experience with drugs on a friday night

hooptyhooptyhoopdehoop — Sat, 05 Jan 2013 21:55:47 -0500

365rulesforpremeds:

medschoolapphell:

Other people:

Me:

I didn’t choose the pre-med life, the pre-med life chose me.

When someone tells me they're majoring in "pre-med"

hooptyhooptyhoopdehoop — Sat, 05 Jan 2013 21:55:43 -0500

medschoolapphell:

Me:

Reading secondary essays that I wrote 5 months ago

hooptyhooptyhoopdehoop — Sat, 05 Jan 2013 21:55:40 -0500

medschoolapphell:

I’m all like:

That point during app season where having multiple acceptances makes you drunk with power

hooptyhooptyhoopdehoop — Sat, 05 Jan 2013 21:55:35 -0500

medschoolapphell:

You start turning down schools like:

The aging process.

hooptyhooptyhoopdehoop — Wed, 02 Jan 2013 10:26:38 -0500

fuckyeahmedicalstuff:

Some age-related physical changes are obvious: an extra laugh line or two, graying hair, and additional weight around the midsection, for instance. But many changes, such as the gradual loss of bone tissue and the reduced resiliency of blood vessels, go unnoticed, even for decades. Even though you’re not aware of them, they’re happening, nevertheless.

Knowing how and why your body changes with age will help you discourage alterations in cell, tissue, and organ function that slow you down. This knowledge will also help you take steps to stop the development of conditions such as diabetes and eye disease that are more common with advancing age.

Since it’s beyond the scope of this article to describe every alteration aging has in store, we’ve decided to concentrate on the major body changes that you may be able to delay -or even prevent - by living a healthy lifestyle, especially by eating right.

Read More

ex0skeletal: Aleksandr Kuskov

hooptyhooptyhoopdehoop — Tue, 01 Jan 2013 11:20:59 -0500

ex0skeletal:

Aleksandr Kuskov

"The Placebo Phenomenon"

hooptyhooptyhoopdehoop — Tue, 01 Jan 2013 11:16:16 -0500

"The Placebo Phenomenon":

aspiringdoctors:

Harvard Magazine article

Two weeks into Ted Kaptchuk’s first randomized clinical drug trial, nearly a third of his 270 subjects complained of awful side effects. All the patients had joined the study hoping to alleviate severe arm pain: carpal tunnel, tendinitis, chronic pain in the elbow, shoulder, wrist. In one part of the study, half the subjects received pain-reducing pills; the others were offered acupuncture treatments. And in both cases, people began to call in, saying they couldn’t get out of bed. The pills were making them sluggish, the needles caused swelling and redness; some patients’ pain ballooned to nightmarish levels. “The side effects were simply amazing,” Kaptchuk explains; curiously, they were exactly what patients had been warned their treatment might produce. But even more astounding, most of the other patients reported real relief, and those who received acupuncture felt even better than those on the anti-pain pill. These were exceptional findings: no one had ever proven that acupuncture worked better than painkillers. But Kaptchuk’s study didn’t prove it, either. The pills his team had given patients were actually made of cornstarch; the “acupuncture” needles were retractable shams that never pierced the skin. The study wasn’t aimed at comparing two treatments. It was designed to compare two fakes.

Although Kaptchuk, an associate professor of medicine, has spent his career studying these mysterious human reactions, he doesn’t argue that you can simply “think yourself better.” “Sham treatment won’t shrink tumors or cure viruses,” he says.

But researchers have found that placebo treatments—interventions with no active drug ingredients—can stimulate real physiological responses, from changes in heart rate and blood pressure to chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and even some symptoms of Parkinson’s.

The challenge now, says Kaptchuk, is to uncover the mechanisms behind these physiological responses—what is happening in our bodies, in our brains, in the method of placebo delivery (pill or needle, for example), even in the room where placebo treatments are administered (are the physical surroundings calming? is the doctor caring or curt?). The placebo effect is actually many effects woven together—some stronger than others—and that’s what Kaptchuk hopes his “pill versus needle” study shows. The experiment, among the first to tease apart the components of placebo response, shows that the methods of placebo administration are as important as the administration itself, he explains. It’s valuable insight for any caregiver: patients’ perceptions matter, and the ways physicians frame perceptions can have significant effects on their patients’ health.

For the last 15 years, Kaptchuk and fellow researchers have been dissecting placebo interventions—treatments that, prior to the 1990s, had been studied largely as foils to “real” drugs. To prove amedicine is effective, pharmaceutical companies must show not only that their drug has the desired effects, but that the effects are significantly greater than those of a placebo control group. Both groups often show healing results, Kaptchuk explains, yet for years, “We were struggling to increase drug effects while no one was trying to increase the placebo effect.”

Last year, he and colleagues from several Harvard-affiliated hospitals created the Program in Placebo Studies and the Therapeutic Encounter (PiPS), headquartered at Beth Israel Deaconess Medical Center—the only multidisciplinary institute dedicated solely to placebo study. It’s a nod to changing attitudes in Western medicine, and a direct result of the small but growing group of researchers like Kaptchuk who study not if, but how, placebo effects work. Explanations for the phenomenon come from fields across the scientific map—clinical science, psychology, anthropology, biology, social economics, neuroscience. Disregarding the knowledge that placebo treatments can affect certain ailments, Kaptchuk says, “is like ignoring a huge chunk of healthcare.” As caregivers, “we should be using every tool in the box.”

Western medicine, however, has been slow to agree with him—partly because of his message, and in his case, often because of the messenger. An acupuncturist by training, he is an unlikely leader in the halls of academia. With a degree in Chinese medicine from an institute in Macao, Kaptchuk is one of the few faculty members at Harvard Medical School (HMS) with neither a Ph.D. nor M.D.—“a debit, not a credit at most medical schools,” says Finland professor of clinical pharmacology emeritus Peter Goldman, one of his early Harvard advisers. (Kaptchuk’s diploma is recognized as a doctorate in many states, but not in Massachusetts.) When Kaptchuk came to Harvard in 1995, “he knew about Chinese herbs and healing needles, and he’d written a very fine book on Chinese medicine [The Web That Has No Weaver (1983)],” says Goldman, “but he didn’t know the first thing about how to conduct clinical studies.”

Kaptchuk joined the faculty as an instructor in medicine and apprenticed himself to several seasoned clinicians and investigators. Within a few years, he was winning National Institutes of Health grants and publishing in medicine’s top journals. “What his colleagues saw was a fierce intellect and curiosity,” said Goldman. “He was asking questions no one was asking.”

Ironically, says Kaptchuk, it was his success as an acupuncturist that made him leave the profession for academia. “Patients who came to me got better,” he says, but sometimes their relief began even before he’d started his treatments. He didn’t doubt the value of acupuncture, but he suspected something else was at work. His hunch was that it was his engagement with patients—and perhaps even the act of caring itself.

For his ideas to gain traction with Western doctors, however, Kaptchuk knew he needed scientific proof. His chance would come in the early 2000s in a collaboration with gastroenterologists studying irritable bowel syndrome (IBS), a chronic gastrointestinal disorder accompanied by pain and constipation. The experiment split 262 adults with IBS into three groups: a no-treatment control group, told they were on a waiting list for treatment; a second group who received sham acupuncture without much interaction with the practitioner; and a third group who received sham acupuncture with great attention lavished upon them—at least 20 minutes of what Kaptchuk describes as “very schmaltzy” care (“I’m so glad to meet you”; “I know how difficult this is for you”; “This treatment has excellent results”). Practitioners were also required to touch the hands or shoulders of members of the third group and spend at least 20 seconds lost in thoughtful silence.

The results were not surprising: the patients who experienced the greatest relief were those who received the most care. But in an age of rushed doctor’s visits and packed waiting rooms, it was the first study to show a “dose-dependent response” for a placebo: the more care people got—even if it was fake—the better they tended to fare.

Kaptchuk’s innovative studies were among the first to separate components of the placebo effect, explains Applebaum professor of medicine Russell Phillips, director of the Center for Primary Care at HMS. For years, doctor-patient interactions were lumped into a generic “placebo response”: a sum of such variables as patients’ reporting bias (a conscious or unconscious desire to please the researchers); patients simply responding to doctors’ attention; the different methods of placebo delivery; and symptoms subsiding without treatment—the inevitable trajectory of most chronic ailments. “There was simply no way to quantify the ritual of medicine,” says Phillips of the doctor-patient interaction. And the ritual, he adds, is the one finding from placebo research that doctors can apply to their practice immediately.

But other placebo treatments (sham acupuncture, pills, or other fake interventions) are nowhere near ready for clinical application—and Kaptchuk is not recommending that they should be. Such treatments all require deception on the part of doctors, an aspect of placebo medicine that raises serious ethical questions for practitioners.

This was disturbing for Kaptchuk, too; deception played no role in his own success as a healer. But years of considering the question led him to his next clinical experiment: What if he simply told people they were taking placebos? The question ultimately inspired a pilot study, published by the peer-reviewed science and medicine journal PLOS ONE in 2010, that yielded his most famous findings to date. His team again compared two groups of IBS sufferers. One group received no treatment. The other patients were told they’d be taking fake, inert drugs (delivered in bottles labeled “placebo pills”) and told also that placebos often have healing effects.

The study’s results shocked the investigators themselves: even patients who knew they were taking placebos described real improvement, reporting twice as much symptom relief as the no-treatment group. That’s a difference so significant, says Kaptchuk, it’s comparable to the improvement seen in trials for the best real IBS drugs.

Although this IBS “open-label” study was small and has yet to be replicated, fellow placebo researcher Frank Miller of the department of bioethics at the National Institutes of Health considers it a significant step toward legitimizing placebo studies. But to really change minds in mainstream medicine, Miller says, researchers have to show biological evidence that minds actually change—a feat achieved only in the last decade through imaging technology such as positron emission tomography (PET) scans and functional magnetic resonance imaging (fMRI).

The first evidence of a physiological basis for the placebo effect appeared in the late 1970s, when researchers studying dental patients found that by chemically blocking the release of endorphins—the brain’s natural pain relievers—scientists could also block the placebo effect. This suggested that placebo treatments spurred chemical responses in the brain that are similar to those of active drugs, a theory borne out two decades later by brain-scan technology. Researchers like neuroscientist Fabrizio Benedetti at the University of Turin have since shown that many neurotransmitters are at work—including chemicals that use the same pathways as opium and marijuana. Studies by other researchers have shown that placebos increase dopamine (a chemical that affects emotions and sensations of pleasure and reward) in the brains of Parkinson’s patients, and patients suffering from depression who’ve been given placebos reveal changes in electrical and metabolic activity in several different regions of the brain.

Kaptchuk’s team has investigated the neural mechanisms of placebos in collaboration with the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. In two fMRI studies published in the Journal of Neuroscience in 2006 and 2008, they showed that placebo treatments affect the areas of the brain that modulate pain reception, as do negative side effects from placebo treatment—“nocebo effects.” (Nocebo is Latin for “I shall harm”; placebo means “I shall please.”) But nocebo effects also activate the hippocampus, a different area associated with memory and anxiety. As happened with Kaptchuk’s patients in the “pill versus needle” study, the headaches, nausea, insomnia, and fatigue that result from fake treatments can be painfully real, afflicting about a quarter of those assigned to placebo treatment in drug trials(see “The Nocebo Effect,” May-June 2005). “What we ‘placebo neuroscientists’…have learned [is] that therapeutic rituals move a lot of molecules in the patients’ brain, and these molecules are the very same as those activated by the drugs we give in routine clinical practice,” Benedetti wrote in an e-mail. “In other words, rituals and drugs use the very same biochemical pathways to influence the patient’s brain.” It’s those advances in “hard science,” he added, that have given placebo research a legitimacy it never enjoyed before.

This new visibility has encouraged not only research funds but also interest from healthcare organizations and pharmaceutical companies. As healthcare companies increasingly reward doctors for maintaining patients’ health (rather than for the number of procedures they perform), “research like Ted’s becomes increasingly relevant,” says Minot professor of medicine and HMS dean for graduate education David Golan, a professor of biological chemistry and molecular pharmacology.

This year, the Robert Wood Johnson Foundation, the nation’s largest philanthropy focused on health and healthcare, awarded Kaptchuk’s PiPS program a $250,000 grant to support a series of seminars at Harvard designed to connect placebo experts with researchers in related fields. And the latest findings to emerge from PiPS—a 2012 study showing that genetic variations may explain why only certain people respond to placebo effects—has caught the attention of the Food and Drug Administration.

That study, published last Octoberin PLOS ONE, showed that patients with a certain variation of a gene linked to the release of dopamine were more likely to respond to sham acupuncture than patients with a different variation—findings that could change the way pharmaceutical companies conduct drug trials, says Gunther Winkler, principal of ASPB Consulting, LLC, which advises biotech and pharmaceutical firms. Companies spend millions of dollars and often decades testing drugs; every drug must outperform placebos if it is to be marketed. “If we can identify people who have a low predisposition for placebo response, drug companies can preselect for them,” says Winkler. “This could seriously reduce the size, cost, and duration of clinical trials…bringing cheaper drugs to the market years earlier than before.”

Not all of Kaptchuk’s studies have been so warmly received. Though few academics quarrel with the quality of his research, he’s remained a prime target for such watchdog groups as Quackwatch and The Skeptics’ Society, organizations that question nonconventional medical approaches. (Other well-known targets include Deepak Chopra, Andrew Weil ’63, M.D. ’68, and the late Nobel Prize winner Linus Pauling.) In 2011, he and a team of researchers published a paper in The New England Journal of Medicine (NEJM) that raised the hackles of some of his fiercest critics.

Thatpaper (praised by scholars as one of the most carefully controlled and definitive placebo studies ever done) described a study of 40 asthma patients given four different interventions: active treatments with real albuterol inhalers; placebo treatments with fake inhalers that delivered no medication; sham acupuncture treatments; and intervals with no treatment at all. The patients returned for 12 sequential visits, receiving eachtype of treatment three times—a novel approach in placebo study that created a large amount of data (480 treatments in total) and turned subjects into their own controls (if patients are compared to themselves from one treatment to the next, researchers can eliminate subjects’ individual differences as a variable). The researchers had hoped to find improved lung function with both the real and sham treatments; what they found instead was that only the real treatment yielded results—the others showed no significant improvement. Yet when Kaptchuk’s team measured patients’ own assessments of improvement, the researchers found no difference reported between the real and sham treatments: the patients’subjective responses directly contradicted their own objective physical measures.

To Dr. Harriet Hall, a retired family physician who writes critically about alternative and complementary medicine for such publications as Skeptic Magazine and Skeptical Inquirer,this discrepancy between objective and subjective results is precisely where the danger lies. As she told a reporter for The Atlantic in December 2011, following the publication of Kaptchuk’s NEJM study, “Asthma can be fatal. If the patient’s lung function is getting worse but a placebo makes them feel better, they might delay treatment until it is too late.”

To Kaptchuk’s team, on the other hand, the conflicting results not only reveal important lessons for researchers and clinicians, but illuminate a gap that is central to placebo research. “Placebos have limitations, and we need to know what they are,” Kaptchuk says. “We’d hoped for measurable objective changes in breathing; what we got instead was a more precise diagram of placebo effects and how clearly the ritual of medicine makes people more comfortable.” That in itself is important information, he says. “Our job is to make people feel better,” and though this study was small, “what we’ve really done here is open up a new set of questions.” No one has yet studied how long-term experience with the ritual of medicine might ultimately affect the course of chronic afflictions, he says. “We hope we’ve opened up that path.”

Kaptchuk and his team have begun to take steps in that direction, continuing to ask new questions and push the boundaries of placebo research. A study published online this past year in the Proceedings of the National Academy of Sciences demonstrated that the placebo response can occur even at the unconscious level. The team showed that images flashed on a screen for a fraction of a second—too quickly for conscious recognition—could trigger the response,but only if patients had learned earlier to associate those specific images with healing. Thus, when patients enter a room containing medical equipment they associate with the possibility of feeling better, “the mind may automatically make associations that lead to actual positive health outcomes,” says psychiatry research fellow Karin Jensen, the study’s lead author.

Those findings led to the team’s most recent work: imaging the brains of physicians whilethey treat patients—a side of the treatment equation that no one had previously examined. (The researchers constructed an elaborate set-up in which the doctors lay in fMRI machines specially equipped to enable them both to see their patients outside the machine and administer what they thought was a nerve-stimulating treatment.) “Doctors give subtle cues to their patients that neither may be aware of,” Kaptchuk explains. “They are a key ingredient in the ritual of medicine.” The hope is that the new brain scans will reveal how doctors’ unconscious thought figures into the treatment recipe.

Within academia, Kaptchuk and his fellow researchers have not escaped criticism, but the voices have been few and far between. The most notable appeared in 2001 in the NEJM—the same publication that included Kaptchuk’s asthma study a decade later. In a paper titled, “Is the Placebo Powerless?” two Danish researchers reviewed 114 published studies involving 7,500 patients and questioned both the research methods and the short duration of most placebo studies. Many of the trials reviewed lacked “no-treatment” groups—an important control group missing even in Kaptchuk’s first “pill versus needle” study.

But Kaptchuk’s response to such criticism is perhaps as rare in academia as his pedigree. “If I remember correctly,” said Asbjorn Hrobjartsson, the lead author of that 2001 paper during a recent phone conversation, “Ted was already thinking along the same lines as we were and realized [our paper] pointed out real methodological problems.” When Hrobjartsson came to speak at Harvard a year later, he stayed at Kaptchuk’s home, and in 2011, the two coauthored a paper (with the NIH’s Frank Miller) on biases and best practices in placebo study.

When Kaptchuk talks about Hrobjartsson’s 2001 paper now, he winces, then nods with acceptance. “At first when I read it, I worried I’d be out of a job,” he says. “But frankly, [Hrobjartsson] was absolutely right.” In order to legitimize his findings to mainstream practitioners, the results must be expertly quantified, he acknowledges. “We have to transform the art of medicine into the science of care.”

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