By John Easton

In most clinical trials the targets are patients, volunteers with a disease who sign up for a study to help advance medical knowledge and perhaps lead to better treatments for what ails them. But this week a report in the Archives of Internal Medicine revealed that sometimes the real targets are not so much the patients as the physicians who treat them.

The doctors who agree to participate as investigators in such a trial almost never find out that that they are the trial’s subjects, the ones being studied. Studies of this sort are known as “seeding” trials–kind of like seeding a cloud with particles in order to produce precipitation. The goals of a seeding trial extend beyond measuring the safety or efficacy of a drug to persuading - some would say hoodwinking - the hundreds of doctors who take part in the study to prescribe the drug and become rainmakers for a drug company. So much for informed consent.

Such matters “seldom see the light of day,” explained Caleb Alexander, associate professor of medicine at the Medical Center, who wrote a commentary to accompany the Archives paper, which was authored by researchers at Brown and Yale Universities. “One might think that seeding trials should be illegal,” he said. “They are unethical. They are not illegal.”

No one knows how often this happens. There is only one other recent, well-documented case and it required a lawsuit to come to light.

In this case, the lawsuit was triggered by accusations that the drug gabapentin - AKA Neurontin, approved by the FDA in 1994 for use to control seizures and in 2002 for nerve-related pain - was being marketed for off-label uses, such as for psychiatric disorders. The suit opened the vaults, allowing plaintiff’s lawyers broad access to the drug makers’ marketing plans, eventually resulting in hundreds of millions of dollars in fines.

One small part of the drug’s history was the STEPS trial, short for Study of Neurontin: Titrate to Effect, Profile of Safety. This was an uncontrolled, unblinded trial, launched after FDA approval. It enlisted 772 investigators, many with little or no clinical-trial experience, and 2,759 patients. Even before it began, there were questions about the design. After it was completed, there was the lawsuit, and then there were documents - more than 3,000 of them - correspondence, memos, presentations, market research. The researchers focused on about 400.

What they found met all the requirements for a seeding trial, as spelled out in a 1994 article in the New England Journal of Medicine (PDF) by former FDA commissioner David Kessler and colleagues. “Some company-sponsored trials of approved drugs appear to serve little or no scientific purpose,” they wrote. They are, instead, “thinly veiled attempts to entice doctors to prescribe a new drug being marketed by the company.”

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Countless campaigns have been launched to steer schoolchildren toward healthy habits, and yet rates of childhood obesity and diabetes continue to soar. Celebrity endorsements, catchy catchphrases, and food pyramid redesigns have struggled to combat the allure of fast food and television in the battle for child health in the United States. But with childhood obesity rates tripling in the last 30 years and type 2 diabetes showing up earlier in life, there’s an urgent need for more effective programs to promote nutrition and exercise in kids. One strategy is to create more relevant programs, locally focused and tailored to the culture of the children the program is trying to help.

That approach inspired not one but two child diabetes prevention programs created by Medical Center researchers and tested with our neighbors on Chicago’s South Side. The two programs - called Reach-Out and Power-Up - are siblings, with similar designs, goals, and measures, but in slightly different populations and venues. The pilot studies, both published in recent months, demonstrate the challenges faced by researchers in creating effective, reproducible programs with a local focus…and also offer hope that a successful intervention is possible.

Before the programs could be designed, the first step was to listen. The research team, led by Deborah Burnet, professor of medicine and pediatrics, organized focus groups with overweight children and their parents to learn about their specific obstacles to improving health and gather ideas about the types of physical activity and classes that would appeal to them. For example, the African-American children said they would like to try martial arts and yoga, so instructors for those activities were recruited. The conversations laid the groundwork for programs that would take the unique circumstances of families on the South Side of Chicago into account.

“Nutrition and exercise are both behaviors we do in a social context; in a place, in a neighborhood, in the context of certain social mores and expectations and cultural factors,” Burnet said. “Food, especially - who cooks, where we learn how to cook, how do our tastes get shaped in what we like to eat - those occur in social and cultural contexts.”

While both programs were designed to improve the health and behavior of children, the targets were both the kids and their parents. In Reach-Out, families gathered at a local YMCA for 14 weeks, splitting into separate parent and child groups for the first part of each session and then reconvening for a combined activity. Sessions included grocery store tours, exercise training, cooking classes, and even a family basketball game. Scavenger hunts, relay races, and Family Feud-style review quizzes were used to keep the kids and their parents engaged. But addressing the family’s cooking and eating habits could also be a sensitive topic.

“Feeding is all bound up with caring and love, so it’s very complicated - if you tell grandma she’s not cooking for her grandchildren right, her feelings get hurt,” Burnet said. “So how do you do that in a constructive way so that grandma is valued, but also moves in this healthy direction?”

At the end of the Reach-Out pilot study, published in the Journal of the National Medical Association, the program earned glowing reviews from participants, who said that it helped reduce food intake, steered them toward new fruits and vegetables, and encouraged increased physical activity. However, the clinical improvements were modest, including slight dips in BMI z-score (which scales the measure to child age) and glucose-to-insulin ratio. The incremental changes might mean that very heavy kids need more help to get back to healthy habits, Burnet said: “Kids who are this big probably need a more intensive treatment and intervention than a weekly community-based program.”

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In zoos, keepers strive to preserve as much of the natural experience as possible for their animals. But not everything can be left up to nature behind zoo walls. While encouraging reproduction can be a zoo mission for captive endangered species, other species can’t be allowed to procreate without limits, lest the zoo run out of room for booming families. In primates, zookeepers turn to a familiar method of birth control - the same hormone-based contraception developed for humans. But does putting a gorilla on “the pill” change more than the animal’s ovulation cycle?

This unusual topic was the basis for University of Chicago graduate Anna Sarfaty’s undergraduate research project. For over a year, Sarfaty and her co-authors closely observed four female gorillas at Lincoln Park Zoo, keeping score of sexual, social, and aggressive behaviors to see if hormonal birth control disrupted their normal activity. Published in the journal Zoo Biology with co-authors Susan Margulis and Sylvia Atsalis, the results offer new information for zookeepers on the effects of contraception.

“Zoos don’t want to separate males from females,” Sarfaty said. “So hormonal birth control is a great option, and we know that it works since it’s been given for many years. But researchers like to understand how animals may be acting differently and understand how the behavior we’re seeing might be different from the natural world.”

Unlike most published studies, Sarfaty’s paper can name names - the stars of the experiment were Rollie, Tabibu, Madini, and Bulera, four of the seven females in the zoo’s gorilla population. Each female gorilla received birth control pills on the same schedule that a female human does - three weeks of estrogen and progestin, followed by one week of placebo pills. Under normal conditions in the wild, gorillas are known to increase certain types of sexual activities known as “estrous behaviors” in the second week of their cycle, near the time of ovulation. So researchers watched their four subjects for 20 minutes a day, four to five times a week, for over a year, to see whether the same behavioral patterns were preserved in the captive, contraceptive-fed females.

Behaviors were scored according to an “ethogram” - a dictionary of behaviors that is “more difficult to write than you would think,” Sarfaty said. The catalog, reproduced in the article, is extensive: listing everything from social play and grooming to biting and chasing to more risque actions such as mounting and masturbation. The researchers also monitored how much time the females spent in the vicinity of the group’s dominant male silverback gorilla, which is a provocative move in gorilla culture.

“Because the gorilla social system is so strict, just sitting close to the silverback male and doing nothing is still a big deal,” Sarfaty said.

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When the media fixates on a medical topic, doctors know that a flurry of patient questions will inevitably follow. So it helps to be prepared with responses to hot-button questions, such as those surrounding the recent resurgence of the potential link between cell phones and brain cancer. Inspired by the World Health Organization moving the radiofrequency magnetic fields produced by cell phones to the classification of “possibly” causing cancer in late May, some newspapers handled the topic with subtle headlines like IS YOUR CELL PHONE KILLING YOU?. Though the fevered media response of some outlets was countered by thoughtful explainers from other sources, many physicians will surely still face questions from patients on the topic. But how does a busy doctor brush up on the extensive literature testing the link between cell phones and cancer?

A: You attend a literature review talk, such as the one given by hematology/oncology fellow Daniel Geynisman at Monday’s installment of the department’s weekly seminar. In half an hour, Geynisman sped through the most important studies examining cell phones and brain cancer, drawing out the important results, criticisms, and implications of the experiments. The primary message was simple - there’s no need to panic, or to go back to using exclusively landlines and pagers. But a true danger does exist with cell phones, Geynisman said, one that’s worth sending a warning to patients - and doctors themselves.

The lingering mystery around cell phones and cancer is caused by an epidemiological quirk, Geynisman explained. Proving the link between a rare exposure and a rare cancer - such as asbestos and mesothelioma - is relatively straightforward. Finding a link between a common exposure and a common cancer is more difficult, but can be done, as it was with smoking and lung cancer. But conclusively proving the connection between a common exposure, such as cell phones, with a rare cancer, such as glioma or acoustic neuroma, is much more difficult. Only about 10,000 new cases of glioma are diagnosed each year in the United States, while more than 300 million cell phones are currently in use in the country. To prove that the use of phones significantly increases brain cancer rates, enormous numbers of subjects would have to be collected and followed.

Those challenges have forced most researchers into a flawed study design, Geynisman said. Retrospective case control studies are commonly used in epidemiology, but are subject to an important confounding factor called recall bias. If you ask 3,000 people with brain tumors and 3,000 controls about their history of cell phone use, those with  cancer are more likely to remember and report unusually high amounts of use. In one study, subjects were found to over-estimate their cell phone use by almost three times, adding a hefty dose of salt to any case control results.

Despite this issue, early case control studies found a relative risk of 1, indicating no increased or decreased risk for brain tumors in users of cell phones. But the question did not go away, fueled by the research of a Swedish group who dialed the data down to find increased risk among very specific groups: people who used cell phones for more than 10 years, or people who started using the phones before the age of 20. The INTERPHONE study, which surveyed over 6,000 people with brain tumors and 7,000 controls from 13 countries, might have settled the dispute but for one result. Published last year, most of the risks calculated for various groups and tumors showed a negative association with cell phone use, suggesting (improbably) that talking on the phone protected against brain cancer. But one association still stuck out - heavy cell phone users showed a 40 percent increase in the risk of glioma. Statistical anomaly, or cause for concern?

The result was apparently enough for the WHO to place cell phone radiation in the same group as other potentially carcinogenic compounds ranging from lead and coffee, and for more studies to be conducted, Geynisman said. After all, ubiquitous cell phone use is a relatively recent development, so more time may need to pass before the health effects can be accurately assessed. A prospective study, called COSMOS, will tackle some of these questions, as it follows a quarter-million subjects for at least 25 years and measures cell phone use as it happens, instead of through memory. But while scientists, physicians, reporters, and the general public wait for those results, they can caution the world about the real dangers of cell phones, which have nothing to do with cancer.

“What’s not shaky is that cell phone users are four times more likely to be distracted drivers and texting poses a risk of 23 times more collisions. 81 percent of Americans use their cell phones while driving, and almost a third of crashes involve cell phones,” Geynisman said. “So you can keep using your cell phone probably, but don’t do it while driving.”

By Dianna Douglas

Darryl Williams got winded while running an annual 10K race in Oak Park in 1995. Puzzling, since he was in excellent shape. Over the next five years, he had irregular heartbeats and felt strange sensations in his chest. But none of the treatments his doctors tried made a difference.

Allen Anderson, associate professor of medicine and director of the Advanced Heart Failure Program, met Williams in 2000. The arrhythmia was becoming life-threatening. Anderson diagnosed Williams with sarcoidosis of the heart, an inflammatory disease, and began to treat him with medication.

Williams was determined to get better. He followed his doctor’s orders and took his medications, even when they had toxic side effects. “We were able to control it for 10 years,” Anderson said. “He did his part as well, by taking care of himself.”

But Williams’ sarcoidosis continued to grow. The disease, which affects about 18 people per 100,000 annually, spread to his liver. Soon his ailing heart and liver put serious strain on his kidneys. Anderson decided that his only hope was a new heart, liver and kidney. “He was in heart failure and liver failure. He was critically ill. He was going to die.”

The criteria to be considered for a three-organ transplant are stringent. “We have to be very careful about patient selection,” Anderson said. A heart, liver and kidney transplant is a massive surgery. “We have to pick patients who have a good chance of survival.”

Williams’ case was the subject of many multidisciplinary meetings, with hematologists, surgeons, nutritionists, psychiatrists, social workers, infectious disease specialists. “The fundamental question is: are you going to commit organs to this person?” said John Renz, professor of surgery and director of the Liver Transplant Program. “You have to look at all aspects of a patient. And you have to feel that you are committing that precious resource well.”

After multiple screenings, the team was convinced. At 55 years old, Darryl Williams didn’t have any other health problems that would complicate his recovery. He was always careful to follow his doctors’ instructions, and would likely keep taking his medications after a transplant surgery. And, as important as anything, he had a large family and community of friends to support him through the ordeal.

After three months of waiting in the hospital for the transplants, Williams was rolled into an operating room.

“It’s an extraordinary surgery,” said Valluvan Jeevanandam, professor and chief of cardiac and thoracic surgery. “People don’t do well after any open heart surgery without a good functioning liver,” he said. “The liver has to filter out toxins and promote coagulation. Similarly, a new liver won’t do well without a good heart.”

He compares multi-organ heart transplants to “walking a tight rope without a net under you.”

There are other pressures, too. After leaving the deceased donor, the heart is only good for about five hours. A liver can be transplanted for 18 hours, and a kidney can sometimes be good for up to 48 hours. So, the heart goes in first.

“From a technical point of view, all three surgeries have to be perfect,” Jeevanandam said. “The challenging thing is sewing in all three organs in an environment hostile to any transplant procedure.”

The heart transplant was over in about four hours, but the heart was struggling. “We had to maintain his heart until he could get his liver,” Jeevanandam said. The surgeons used inotropes to stimulate the heart and a balloon pump to keep oxygen flowing.

Then Renz and the liver transplant team took over. read more

Around the pediatric cancer wards at Comer Children’s Hospital, he was known by the rhyming nickname of “Doc Nach” and for delighting patients with his Mickey Mouse watch. On a ward where a smiling face goes a long way, Dr. James Nachman was always happy to provide a cheerful presence. Behind the scenes, he was also a dogged researcher, developing new protocols for children who didn’t respond to the standard treatment for acute lymphoblastic leukemia (ALL) and working to save the limbs of children diagnosed with sarcoma, a cancer of the bones.

Sadly, Nachman passed away last week at the age of 62, while on a rafting trip in the Grand Canyon. This week, Medical Center colleagues remembered “Doc Nach” for his skill with patients and scientific expertise.

“Jim was an outstanding clinician, teacher, and clinical researcher,” said John Cunningham, professor of pediatrics and chief of pediatric oncology. “He made seminal observations in leukemia and lymphoma that have impacted the lives of many children and adults with these diseases. He was an outstanding doctor, beloved by his patients, their families, and his colleagues. He was an irreplaceable member of our cancer team. We will miss him deeply.”

Patients’ families also were quick to pay tribute to Nachman. At the ChicagoNow blog “Ay Mama,” Laura Lutarewych wrote a moving post about her encounters with Nachman during the treatment of her 2-year-old daughter, Atia.

He’d walk into a room with a smile asking, “How’s my favorite girl?” It didn’t matter who the patient was - they were all his favorite, so it was fitting and each child wore their title proudly.

Without exception, he’d hold out his wrist and ask, “Who’s on my watch?” Atia especially loved that part, because she knew the script; she didn’t even have to look at the watch. With a huge smile, she’d point at it and exclaim, “Mickey Mouse!”

Earlier this year, we shot a video with Nachman for a series of informational segments on pediatric cancer topics that you can view below. Even in answering technical questions about how ALL is diagnosed and treated, you can see the good cheer and optimism in Nachman’s demeanor that was so comforting to his patients. For all of the people he touched during his life, that positive attitude will be missed.

“He was an optimistic, sunny person,” his brother Robert Nachman said in the Chicago Tribune obituary, “and his eyes lit up whenever he was talking about children.”

Elsewhere…

Linkage was off last week, so we didn’t have a chance to post this excellent front-page Chicago Tribune article about the neuroprosthetics research program here at the University of Chicago. Reporter Cynthia Dizikes also penned an online supplement that explains the link between assistant professor Sliman Bensmaia’s favorite Star Wars scene and his research on the neural mechanisms of touch.

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Most people turn to Google to search for news on Justin Bieber, baseball scores, and who got kicked off Top Chef last night. But users of the search engine also turn to Google for medical advice, typing in symptoms and conditions as a sort of pre-screening tool before making the call to the doctor’s office. These health-related searches inspired the creation of Google Flu Trends, an official tool of the website that estimates influenza incidence and spread via the dynamics of searches for flu symptoms, medications, and other related terms. With some complicated mathematics, Google developed a formula predicting flu activity that closely matched actual surveillance data, an achievement deemed worthy of publication in Nature.

The success of Google Flu Trends have prompted scientists to wonder if other diseases can be similarly watched by tracking search engine data. But while everyone knows about the flu (even if it is often mistakenly blamed for illnesses caused by other bugs), more obscure diseases might not be as easily captured by such a strategy. Take the case of methicillin-resistant Staphylococcus aureus, the medical mouthful better known as MRSA. Though MRSA is the most common cause of human infections, with 94,000 cases in 2005, it isn’t usually part of the layperson’s medical vocabulary. But because the CDC surveillance system for MRSA only covers 9 sites, a team of researchers from the University of Chicago and the University of Colorado set out to see if Google searches would suffice as a higher resolution alarm system for public health observers.

“If we had a comprehensive, linked electronic-health-records system that researchers had access to, we wouldn’t need it,” senior author Diane Lauderdale, professor of epidemiology, told Wired. “There are systems like that in Scandinavian countries, where you can analyze disease factors in all kinds of ways. But you can’t do that in the U.S.”

As reported in Emerging Infectious Diseases, Lauderdale, Vanja Dukic and Michael David measured the frequency of Google searches for “MRSA” and “staph” (because many news stories refer to the bacteria as drug-resistant or antibiotic-resistant staph) between 2004 and 2008. The group also charted appearances by MRSA in the media, to control for the influence of the news upon searches, and used data from a consortium of hospitals to serve as a measure for MRSA hospitalizations over the time period. Other challenges, such as the frequent mis-spelling of “mersa” and the infrequent correct spelling of “methicillin” were also taken into account.

The data showed a steady rise in the number of searches for MRSA, staph, and even “mersa” that mirrored the increase in hospitalizations for MRSA over that same time period. Surprisingly, media reports about the drug-resistant bacteria were not very influential on the number of searches, except for the coverage of a 2007 CDC report that MRSA caused nearly 19,000 deaths in the year 2005 - which prompted a spike of Googling. As such, the team was able to create a model using the Google queries that predicted the rate of MRSA hospitalization with considerable accuracy, as reflected by the red and pink lines in the graph above.

Interestingly, Google searches for MRSA steadily increased at the same time as one group of MRSA infections declined. A study published last year examining the rates of hospital-acquired or health care-associated MRSA cases found a reduction from 2005 to 2008 as medical facilities stepped up preventative measures against the bacteria. The Google trend may thus reflect increases in the more alarming community-acquired form of MRSA, as spotlighted in Maryn McKenna’s Superbug. With a new prediction model, public health experts can keep an eye on the search engine trends to try to pinpoint outbreaks, even on a local level, before patients begin arriving in hospital emergency rooms with severe infections.

“If we knew the rate was two or three times higher in one city than another, that could be an influence on public health campaigns,” said Lauderdale in Wired.

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Dukic VM, David MZ, Lauderdale DS. Internet queries and methicillin-resistant Staphylococcus aureus surveillance. Emerg Infect Dis. 2011 Jun

More and more Americans are working at least a portion of their jobs from home, facilitated by technological advances and encouraged by soaring gas prices. Even physicians, enabled by the spread of electronic health records (EHR), are increasingly able to perform some of their tasks at home, including updating patient records, checking lab results, and submitting orders for their patients. But for residents - the doctors-in-training who log the longest hours in the hospital - the ability to work at home can add even more burden to an already overstuffed schedule. In light of new national duty hour restrictions which limit residents to 80 hours a week, there could be increased pressure to push even more of their work to the home office.

However, few studies have looked at just how often these clinical activities already occur from home. To fill this gap, a team of Medical Center residents recently conducted a survey about the frequency of clinical and educational work done at home by their peers. The results of that study, published yesterday in the Archives of Internal Medicine, depict the double-edged sword of EHR home access: greater convenience and surveillance mixed with the potential for danger and abuse - especially as the new rules go into effect on July 1st.

“There are constantly new restrictions on duty hours but additions and new requirements in our training, which include more clinic time,” said Allison DeKosky, one of the study’s authors. “So we’re constantly logging in from home, not just to look up information for our research and education on our own time, but also to follow up on patient information that we simply couldn’t do in the hospital because we had to leave.”

The survey, conducted at two Chicago hospitals, found that performing clinical duties at home is commonplace. A majority of residents reported checking and ordering labs, reviewing records, e-mailing or paging staff at the hospital, and conducting clinic phone calls and orders at least once per month. Of more concern, significant numbers reported performing such activities at least once on their post-call day - when residents are supposed to be recovering from a grueling 30-hour hospital shift.

“Working from home is not necessarily always bad,” said Vineet Arora, associate professor of medicine and faculty advisor on the study. “After all, with electronic health records, working remotely is part of modern-day physician practice. The key question for residency programs is where do you have to draw the line and say that’s unsafe.”

The potential missteps are many: sleep deprivation could interfere with medical decision-making, the information received via EHR may be incomplete or out-of-date, and orders from the resident at home and the team working in the hospital could be redundant or conflicting. So why do residents have such a tough time leaving their work at work? DeKosky said that it’s a combination of responsibility, communication concerns, and looking out for their fellow residents. When shifts change after a call shift, the resident must turn their patients over to another resident to cover in addition to the incoming resident’s own patient load. Not wanting to over-burden the cross-cover resident or worried that an important test result or order might get lost in the shuffle, the post-call resident may feel compelled to check in via the EHR from home.

“It’s hard for us to relinquish responsibility for our patients, we all care very much about them,” DeKosky said. “It is a balance between getting out of the hospital and maintaining your ownership of the patient.”

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The treatment of cancer is growing more and more specialized, as researchers and pharmaceutical companies test strategies designed to attack very specific types of tumors. A success of this approach received an avalanche of publicity this past week at the American Society for Clinical Oncology meeting in Chicago - two new drugs that target mutations associated with some forms of melanoma. But the history of cancer treatment is marked by many happy accidents, and two papers published shortly before the ASCO meeting revealed a potential new bit of cancer-fighting serendipity. In this case, a drug class used for decades to treat hypertension and heart disease may play a previously-unanticipated role in improving the outcome of patients with breast cancer by interfering with the more general phenomenon of stress.

Beta blockers are a group of drugs named for their inhibition of the beta-adrenergic receptors, where the hormone known as adrenaline or epinephrine binds and activates the sympathetic nervous system. Drugs that block these receptors can lower a patient’s heart rate and blood pressure, making them valuable tools for fighting cardiovascular disease. Those effects would seemingly have little to do with treating cancer. But animal and tissue culture studies have suggested a role for beta-adrenergic receptors in promoting tumor growth and metastasis, and human data implicating lifestyle factors such as social stress and obesity in cancer outcomes have also suggested a role for the sympathetic nervous system.

Those were enough clues for two groups of researchers to test whether beta-blockers affected the usual course of breast cancer. Using retrospective data on thousands of patients from the United States or Ireland, the two groups compared patients who were taking beta-blockers (for reasons unrelated to cancer) and women who were not on the drugs. While retrospective studies aren’t always the best way to measure the effect of an intervention - due to an inability to control what data was collected, which beta blocker was used, how much of the drug was given, etc. - it was a fast way to see whether promising signs were apparent in a large population.

In spite of these limitations, both studies (published in late May in the Journal of Clinical Oncology) found favorable effects of beta blockers in breast cancer patients. In the United States study, led by former Medical Center fellow Amal Melhem-Bertrandt and co-authored by professor of medicine Suzanne Conzen, women with triple-negative breast cancer who were on beta-blockers during their cancer treatment exhibited a longer relapse-free survival, despite no dramatic differences in initial tumor response to chemotherapy. The effect on patient’s cancer-free survival was particularly notable, since triple-negative breast cancer is a form of the disease especially prone to relapse and death.

“It seems to be particularly affecting those tumor cells that are left behind after chemotherapy and surgery, those that grow back  after the initial therapy and return as recurrences,” Conzen said. “It suggests that the beta-adrenergic pathway has something important to do with tumor growth and the stress responsiveness of the tumor cells themselves.”

The study using breast cancer data from Ireland found benefits of beta-blockers using slightly different measures. Women who were on beta-blockers were initially diagnosed with less severe tumor types and displayed significantly lower breast-cancer related mortality than the no-drug controls, the authors reported. Intriguingly, they also determined that one type of beta blocker, propranolol, produced these protective effects while a more specific version, called atenolol, did not show an effect.

The authors of an editorial appearing alongside the two articles were convinced enough to call for “proof-of-concept” trials to more carefully test the value of beta blockers in treating breast cancer. But Conzen said the star of the show was not necessarily the drugs themselves, but the identification of a stress response pathway with an impact upon cancer outcomes. With professor of psychology Martha McClintock, Conzen’s laboratory is studying the relationship between stress and breast cancer in animal models, and the new studies add an intriguing piece to that puzzle.

“It fits our hypothesis that a patient’s chronically heightened stress responsiveness resulting from exposure to unrelenting stressors is associated with increased breast cancer growth,” Conzen said. “We think that the new beta-blocker results reflect the beneficial effect of antagonizing part of this pathway.”

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By Dianna Douglas

More research practically begging people to get a good night’s sleep has come out of the sleep labs at the University of Chicago. Eve Van Cauter and Rachel Leproult have discovered that a week of inadequate sleep means less testosterone in young men.

A lot less.

In the study, ten healthy young men gave blood samples after a week of sleeping just five hours a night. By the end of the week, they had 15 percent less testosterone than normal. “This is not an insignificant amount, since it is about the amount that occurs with normal aging by 10 to 15 years,” Van Cauter said. As a man ages, testosterone production decreases by 1 to 2 percent a year.

The lack of testosterone affected not only the reproductive function of these young men, but their happiness as well. Testosterone is a vital hormone for a man’s physical and mental health, and is released into the body during sleep.

“Low testosterone levels are associated with reduced well being and vigor,” Van Cauter said, explaining why the young men said they felt grumpy and lethargic, and their mood worsened as the study progressed.

Low testosterone is associated with low energy, reduced libido, and poor concentration. Consumer Reports Health found in a recent survey that feeling too tired is the reason men cite most often for a low sex drive.

This isn’t just a lab exercise - sleep loss is endemic in modern society. At least 15 percent of the adults in the US get less than 5 hours of sleep a night. Shift workers are especially at risk for lost sleep. The average American got nine hours of sleep in 1910 and got seven in 1975. The cumulative effects of short sleep are still being discovered, and they’re all bad. People who don’t get enough sleep are fatter, more likely to have diabetes, have all sorts of learning and cognitive problems, and die earlier. Van Cauter says that a nation that doesn’t sleep enough has an epidemic of obesity and diabetes.

“As research progresses, low sleep duration and poor sleep quality are increasingly recognized as endocrine disruptors,” Van Cauter said. Mess with the delivery of hormones throughout the body, and people become hungrier and sadder. Their blood pressure goes up and their insulin production goes haywire.

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By Meghan Sullivan

That there even was a luncheon at Crerar library last week to welcome Nancy Hopkins was a sign of progress. Speaking of a committee formed at MIT in 1995 to explore gender discrimination among tenured faculty, she commented that their meetings were generally held off campus since “having that many women in one room at MIT was so unusual that we were afraid to be seen meeting on campus…it was sure to arouse suspicion.”

Fifteen years later, the packed luncheon in the middle of Crerar was hard to miss. A few dozen women - and a few men - had gathered to discuss her work uncovering and fighting gender discrimination at MIT. More than a relaxed opportunity to ask Hopkins questions before her afternoon lecture, the lunch was a chance for graduate students and post-docs to discuss their experiences and ask for advice. While the prevalence of gender discrimination in the sciences and elsewhere tends to incite strong emotion, Hopkins carried herself with sensibility and humor that was contagious.

Hopkins, a professor of biology at MIT and accomplished cancer biologist, is the first to admit that she never intended to be a feminist. It wasn’t until pervasive and arguably unconscious barriers at MIT began to impede her research in 1995 that she took action against the status quo. Science, she pointed out, has always been touted as a meritocracy, yet she saw her female colleagues repeatedly passed over for tenure, funding, even lab space. In the early stages of her work on gender discrimination, Hopkins perused the MIT staff listings looking for other women in science. She was shocked to learn that out of 274 faculty positions, only 22 were filled by women. “I said check the back of the catalog,” she laughed, “Perhaps they list them separately.”

But why was science losing women? By the nineties the percentages of male and female graduate students in the sciences were about equal, yet that equality failed to emerge in tenured faculty positions. To explain this, Hopkins described a well-established phenomenon known as “the Leaky Pipeline.” In essence, while the proportions of male and female students entering science are comparable, women are more likely to leave (or leak out of) the scientific career path due to issues which primarily affect women.

Like many, Hopkins believed the Civil Rights Act and affirmative action policies were the answer to getting more women in science. But over the next thirty years, less obvious issues proved serious barriers, including sexual harassment, connecting with an empowering mentor, and managing a successful family-work balance. The last was especially frustrating, as high level science can often require more than 70 hours of work a week, leaving little time for family and children. As Hopkins put it, many were required to be “nuns of science,” working in an environment where talking about family and children was far from the norm.

However, it wasn’t until one of the more insidious barriers to women in science began to interfere with Hopkins work that she got involved. Called unconscious gender bias, this subconscious undervaluation of work done by women has been studied for years by psychologists. For example, when people are shown work done by a man or a woman and asked to rate it, the panel will value the man’s work over the woman’s, even if the objective quality of both is identical. Such undervaluation of women’s work not only directly impedes their progress up the academic hierarchy, but also self-selects female researchers out of science, caving to feelings of inadequacy and disappointment. As Hopkins said, she felt that “no matter what I discovered, I wouldn’t be accepted in this field.”

Rather than give up a career she’d already sacrificed so much for, Hopkins and 16 other tenured female faculty members drafted a letter to MIT’s Dean of Science at the time, Robert Birgeneau, concerning the unfair gender biases prevalent in the MIT system. Birgeneau responded immediately and impressively to the committee’s report, instituting an aggressive hiring campaign designed to recruit top female researchers from around the world. The resulting increase in the percentage of women faculty was fondly called “the Birgeneau bump.” In addition to the hiring of more women, MIT set to work on increasing day care options and set up committees that would oversee equality in working conditions and institutional policy. These institutional changes would go on to become a standard in the academic world and be adopted by institutions throughout the country.

Yet problems remain.

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By John Easton

Are we flushing away cures? In the last few years, physicians have developed a new respect for what used to be considered waste. Led by a maverick Australian physician, many US doctors have begun to test the curative capacity, when appropriately acquired, prepared and administered, of human excrement.

For once, it’s not the fiber that interests these digestive specialists; it’s the creatures that live in it, the intestinal flora. These indwelling microbes, when compared cell-to-cell, outnumber their hosts by about 10 to one. More than 1,000 different strains of bacteria co-exist peacefully in the typical healthy bowel. But when the delicate balance is altered by antibiotics or other causes, a few strains can become dominant, leading to severe diarrhea, inflammation, tissue damage, even death.

Bacterial aggregates derived from fecal matter have been used sporadically to treat digestive disease for more than 50 years. These were often last-ditch efforts aimed at restoring microbial balance for patients with raging intestinal infections. Fecal microbiota transplantation (FMT) - also known as fecal bacteriotherapy, among other names - is designed to calm a troubled bowel by reintroducing the vast diversity of collaborative bowel inhabitants after the usual, collegial mix has been disturbed.

The first FMT cases, dating back to 1958, were used to treat life-threatening infections caused by aggressive bacteria that had overwhelmed the bowel and eradicated the competition. When antibiotics were unable to control the infection, physicians were able to restore balance by collecting fecal matter from a healthy donor and injecting it into the patient’s colon. It was like a massive dose of probiotics, but delivered bottom up, rather than top down.

More recently, the approach has produced lasting remissions for a small number of patients with a common disease: ulcerative colitis. In 2003, a team led by the Australian physician, Thomas Borody, published a report [pdf] on successful treatment with this approach of six patients who had longstanding ulcerative colitis (UC). “Complete reversal of UC was achieved in all 6 patients following the infusion of human fecal flora,” the authors reported. “These 6 cases document for the first time the total disappearance of chronic UC without the need for maintenance treatment.”

After interviewing Borody, the Freakonomics podcast summarized the expanding medical role of human feces like this: “To paint it with a very broad brush: it could be that many maladies - from intestinal problems to obesity to disorders like multiple sclerosis and Parkinson’s and Alzheimer’s and perhaps even cancer - are related to damaged or missing gut bacteria; the solution therefore may lie in transplanting healthy bacteria into a sick person.”

“This is a fascinating idea, and the early studies show great promise,” said University of Chicago gastroenterologist David Rubin, associate professor of medicine. The notion has also made headway among patients. “We are getting at least one phone call a week from patients asking about the treatment and when we are going to start treating patients,” said colleague Stacy Kahn, instructor of pediatrics at the University of Chicago.

Although fewer than a dozen case reports involving ulcerative colitis have been published, Rubin and Kahn realized that many more patients were getting treated, largely without supervision or medical oversight, a development they called “alarming.” Several websites now provide guidance, almost like recipes, on how to perform this relatively simple procedure.

“This morning I decided to try a fecal transplant,” begins the saga of “Lucky Lindy,” posted on HealingWell.com. “I’ve been reading about it for months, and figured I might as well try … and while the process was a little gross it was easier than I anticipated. For anyone who is interested (and not grossed out), below is the process I used.” He goes on to list his entire protocol, with daily progress updates and cost-cutting tips, such as using a fork to stir the broth instead of a difficult-to-clean blender. read more

In the 2000s, a new kind of genetic experiment was born: the genome-wide association study, or GWAS. If geneticists could recruit enough people with a particular disease and compare them to an equal number of disease-free controls, they believed GWAS would point the way to common gene variants associated with disease risk and novel biological pathways. One of the strengths of GWAS was that it was hypothesis-free, an unbiased comparison that could reveal surprising risk-associated genes that had not occurred to scientists in the past. More than 1,000 GWAS studies have been conducted to date, on diseases ranging from diabetes to Parkinson’s disease to Crohn’s disease to various types of cancer.

While these studies have identified thousands of gene variants (called single nucleotide polymorphisms, or SNPs) associated with disease risk, they can still only explain a small fraction of the heritability of disease. Some scientists have thus moved on from GWAS to the next wave of genetic studies, including whole-genome sequencing to look for rare variants and gene-environment interaction studies. But some geneticists think the field may be moving too quickly onto the next big thing, and that there remains value in the volumes of GWAS data collected over the last decade. A second generation of GWAS is taking place, where the data from the first round is approached in new ways to find previously hidden gems of information.

In two recent studies, assistant professor of health studies Brandon Pierce applied this Reuse/Recycle/Reduce philosophy to GWAS data on pancreatic cancer risk, a disease where genetic and biological explanations are particularly lacking. For both experiments, Pierce bended the “hypothesis-free” rule of GWAS in order to narrow the field of gene variant candidates and allow for a more selective scan of pre-existing data. By reducing the number of candidates from the ~550,000 of a full GWAS, the statistical threshold for confirming a SNP association with risk can be set lower. If the original GWAS experiments were the equivalent of looking for a needle in a haystack, the new techniques are a much less daunting task, he said.

“You conduct fewer tests, so the haystack is smaller,” Pierce said. “In all of the tests you are conducting, you know the SNPs are biologically meaningful, whereas in a typical GWAS, a large percentage of the SNPs may have very little to do with human biology.”

In the first study, published in March in Cancer Causes & Control, Pierce adapted a connection discovered by epidemiology studies to his genetic scan. Patients with type 2 diabetes were measured to have elevated risk for pancreatic cancer - a logical relationship given that diabetes is primarily a disease of the pancreas. Pierce took 37  SNPs associated with type 2 diabetes and tested them in the GWAS data collected by a previous study of pancreatic cancer. None of the SNPs tested showed a strong association with pancreatic cancer, though two new gene variants produced suggestive evidence of an association. The results suggested that the biological link between type 2 diabetes and pancreatic cancer may not be as strong as the epidemiology data indicated.

“We didn’t find any major associations that popped out at us from the diabetes study, so the conclusion was that these established genes for type 2 diabetes don’t seem to have a big effect on pancreatic cancer risk,” Pierce said.

But a second study, published in Cancer Research, would lead Pierce almost full circle. This time around, he ran the pancreatic cancer GWAS data through what he dubbed a “pleiotropy scan,” testing only SNPs previously demonstrated to have a biological effect in humans. For many of the more than half-million SNPs typically tested in a GWAS, scientists have yet to discover a linkage to any disease or biological effect, suggesting that these markers may sit without effect in the long gaps between protein-encoding genes in human DNA. Like the first study, limiting his GWAS tests to only these SNPs (1,087 in this case) allowed Pierce to pick up more subtle associations than in a full-blown GWAS.

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Teaching with Treadmills

Inside the Biological Sciences Learning Center on the Medical Center campus is a laboratory that looks more like a gymnasium. Six state-of-the-art treadmills and six futuristic exercise bikes sit around the room, each connected to a computer alongside modified oxygen masks and suction cup sensors. Instead of dissecting frogs or mixing chemicals, students show up to lab sections in shorts and running shoes, prepared to sweat for science. In Mark Osadjan’s “Metabolism and Exercise” course, part of a two-quarter Exercise and Nutrition sequence, there’s no sitting on the sidelines.

Since joining the University of Chicago as a senior lecturer in 2003, Osadjan has designed courses that teach undergraduates about biology by connecting with what most college students care about: keeping fit, and sex. As part of the UChicago core curriculum, every undergraduate must fulfill a biology requirement, even if their interests lie in political science, music theory, or philosophy. With his “Metabolism and Exercise” and “The Biology of Gender” courses, Osadjan has met these science-shy students halfway, filtering instruction on evolution, physiology, and genetics through their own personal hobbies and interests. The efforts have been such a success that Osadjan’s courses fill up soon after registration is opened.

Today, Osadjan was announced as one of this year’s recipients of the Quantrell Award for Excellence in Undergraduate Teaching, an esteemed UChicago honor that goes back to 1938. Last week I met with Mark to talk about his award and his career path, from a graduate student studying Antarctic fish to an instructor of graduate-level science to his current position, teaching predominantly undergraduate non-biology majors.

“It’s always a trick to figure out how to teach with enough enthusiasm, such that it spills over to the students,” Osadjan said. “It’s our challenge not only to teach these students a certain number of facts, but to show them why those facts are important, relevant, and worth thinking about throughout life.”

You can read more about Osadjan and the other Quantrell winners in the award package at The University of Chicago news site.

Elsewhere…

Most college students spend their summers traveling the country or working an internship, but 20-year-old Rachel Garneau had other plans: donating a kidney. On Tuesday morning, Garneau came to the Medical Center and made the rare gift of an altruistic kidney donation, triggering a kidney swap chain that helped patients in need of the organ in New York and Madison. Neil Steinberg at the Chicago Sun-Times followed the story before and during the surgery, and got some great play-by-play commentary from Yolanda Becker, professor of surgery and director of the kidney and pancreas program.  For instance: “‘The pancreas is the bitch of the abdomen,” she confided.’”

Are clinical trials handicapped by their own success? A new analysis from Anup Malani and Tomas Philipson of the University of Chicago Law School finds that trial enrollment for a given disease plummets when a treatment is found to be effective, using AIDS clinical trials after the approval of anti-retroviral therapy to illustrate the point. Richard Schilsky, professor and section chief of hematology/oncology at the Medical Center, agreed with the findings at Nature News: “There are so many options that patients are not flocking to get into clinical trials like they used to.”

Read how turtles move to warm areas to bask - even in their own eggs as embryos. Adorable photos and interesting commentary (are they determining their own sex?) at Not Exactly Rocket Science.

That news about the World Health Organization adding cell phones to their list of possible carcinogens? Here’s an article from Cancer Research UK to reassure your fears. Another reassuring fact: it was placed by the WHO into the same risk category [pdf] as coffee, dry cleaning, and pickled vegetables.

Can jazz musicians tell the difference between another musician improvising or following composed music? A new study finds the answer, and a ScienceNOW article gives you the chance to test yourself.

Did you know UChicago evolutionary biologist Neil Shubin does a regular science news roundup on local newsmagazine show Chicago Tonight called Scientific Chicago? Well he does, and the latest edition discussed a story familiar to readers of the blog: the mass extinction 360 million years ago that ended “The Age of Fishes.” Watch the video here.

The final question of the MacLean Center for Clinical Medical Ethics seminar series on health disparities was a seemingly obvious query that had gone unasked and unanswered the entire year: who is responsible for fixing the problem? For the self-selecting audience that had attended the lectures all year, the question may have seemed irrelevant - many in attendance are already working on research and interventions to reduce disparities at home and abroad. But for Dan Brock, the director of medical ethics at Harvard Medical School, the question was worth approaching from a philosophical perspective, if only for the purpose of preaching beyond the choir assembled each week at the seminar series.

The statistics about disparities between developed and undeveloped countries are not in question: the threefold difference in life expectancy, the millions of children who die each year from preventable disease and malnutrition, the large discrepancies in health care spending. But who has the moral responsibility to try and remedy these enormous global health gaps? Is it the obligation of rich individuals, or organizations and institutions, or governments, or (as a libertarian might say) of nobody at all? Brock said that philosophical theories of global justice are too new to offer answers for such questions. Arguments have been made for centuries about helping the unfortunate you can see, or even the unfortunate of your own tribe, city, state, or country. But stretched to a global scale, these theories have not yet matured, on issues such as how to take care of a nation’s own needy while still assisting the “foreign” needy thousands of miles away.

To address this shortcoming, Brock suggested three other scaffolds upon which an argument for fighting global disparities could be argued. The first was an economic proposition: as he stated, “if you can prevent great harms at little risk, you are obligated to do so.” Fifteen cents worth of rehydration salts can save a child from dying of dehydrating diarrhea, ten dollars (the cost of a movie) given to a charity can buy minimum essential medicines and more - an argument for sacrifice.

“One can’t make a plausible case that more good comes from me going to a movie then would be done in the world if I had gave that money to OxFam instead,” Brock said.

One obstacle to these small acts of charity is the “out of sight, out of mind” phenomenon - as Brock said, almost everyone would give part of their sandwich to a starving African child sitting next to them, but the concept of millions of starving African children is more abstract. But in a time of increased connectivity, where news organizations and social media can instantaneously spread images around the world from even the most remote locales, this detachment will no longer be an excuse, he said.

Brock’ s second argument that the well-off are obligated to help the needy was a harder pill to swallow: Guilt. The prosperity of the developed world is not independent from the poverty of the undeveloped, Brock argued; it was built upon a history of slavery and colonialism that has continued to handicap Africa and Asia long after such policies (officially) ceased. Even today, the exportation of natural resources such as oil from Africa and the Middle East to the developed world perpetuates oppressive governments, inequalities, and poverty in those countries. That complicity in the suffering of others gives the developed world a special responsibility to help, Brock said.

“Our failure to act isn’t just a failure of beneficence, a failure to help others that are needy, because we are in significant respects causally responsible for their need and in turn morally responsible for their suffering,” Brock said. “If I was the one who drove into your car and wrecked it, then I have a special obligation to help you, because I caused your need.”

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