As another year comes to a close we’d like to look back at the fascinating research breakthroughs and inspiring patient stories from 2011. ScienceLife ran 168 posts this year, and while we wish we could highlight all of them, here are a handful of our favorites from each month.

January

Patrick Wilson found out that the H1N1 virus could end up helping us fight all types of flu. Stephen Pruett-Jones studied how some male birds mimic the sounds of predators to pick up the ladies (with an audio clip). We interviewed David Gozal about his study on the link between childhood obesity and lack of sleep, and took a look at NCAA regulations mandating sickle cell testing for athletes.

February

Harold Pollack gave a lecture on why violent crime in urban, minority communities should be considered a public health epidemic. Siri Atma Greeley studied the actual medical benefit of widespread genetic testing. Stacy Lindau wanted to know why so few women get help for sexual problems after surviving cancer. We talked to Bana Jabri about the causes of celiac disease, and Sliman Bensmaïa showed us how the brain processes the basic elements of touch very much like it handles visual information.

March

Sola Olopade educated women in Nigeria about using clean-burning stoves to prevent indoor pollution. Stefano Allesina and Jonathan Levine looked at how rock-paper-scissors helps explain evolution. Joshua Miller went to Yellowstone Park to see what stories the ghostly bones of animals can tell, and Scott Eggener questioned the wisdom of indiscriminate prostate cancer screening.

Photo by Gerald Waddell

Andrea King studied the wide range of responses to drinking alcohol, and why it can be fun for some people and a bummer for others. Cheryl Reed took a ride in a helicopter with our UCAN nurses. Kamal Sharma looked at the genes that control animals’ gait, and Ningqi Hou studied how urban environments can dictate how much exercise people get.

May

Daniel McGehee looked at the long-term effects of nicotine on the brain. Habibul Ahsan went to Bangladesh to study the health impacts of accidental exposure to arsenic in drinking water. The brain’s overlooked supporting cells got their due at a conference on neuroscience, and we remembered a landmark discovery about a once popular drug taken during pregnancy that we now know can cause cancer.

June

As we headed into summer, Diana Lauderdale used Google to track MRSA. We learned about an extraordinary transplant where a man received a new heart, liver AND kidney. Daniel Geynisman gave us the rundown on whether or not cell phones are killing us (they’re not, as long as you don’t use them in the car), and some UChicago undergrads studied what happens to gorillas on the birth control pill.

July

We spoke to Donald Jensen and Andrew Aronsohn about the new outlook for patients with hepatitis C. Igor Schneider made a time machine to find the genetic switch for limb development. Farr Curlin led a study about the benefits of addressing spiritual needs alongside medical care, and Adam Cifu looked at the phenomenon of scientific study reversals.

August

Stefano Allesina dug into the long, shady history of nepotism in academia in Italy. John Schneider talked about his work addressing sexual health and stigma in India. Michael Becker discovered a new treatment for the Royal Disease, and we had the rare chance to name check a Spiderman villain in a post.

September

Martha McClintock and Suzanne Conzen studied the connection between social isolation, stress and breast cancer. Gallego Romero traveled to India to search for the origins of lactose intolerance. Stephanie Dulawa developed a mouse model for OCD, and Paul Vezina looked at a different kind of obsession, compulsive gambling.

October

Arshiya Baig started a pilot project to help people learn about life with diabetes through pictures. Manyuan Long found that some of the youngest genes are in the brain. Jens Ludwig and Stacy Lindau published a landmark study about the connection between neighborhood poverty and health, and Issam Awad studied a rare brain disease that soon could be treated with a drug instead of surgery.

November

Cathy Pfister and Tim Wootton figured out how to use seashells to track climate change over the years. Lianne Kurina found a link between loneliness and sleep quality. Shantanu Nundy, Monica Peek and Marshall Chin developed a program to send text message reminders to people with diabetes, and Pan Chen looked at the links between childhood abuse and aggressive behavior in adults.

December

Inbal Ben-Ami Bartal, Jean Decety and Peggy Mason discovered that rats can show empathy for their fellow rats in distress. Maciej Lesniak performed a scary but amazing brain surgery on a patient who was awake. Cathryn Nagler searched for the source of food allergies within our bodies, while Stafano Guandalini uncovered the challenges in educating doctors about one of those allergies, celiac disease.

Whew. Hope you were able to click through at least a few of those. We look forward to another great year of research in 2012. We’re taking a break next week, but we’ll be back on January 5. Happy holidays!

When the drug ezetimibe was approved in 2002, it was hailed by its makers as a new tool for lowering cholesterol and fighting heart disease in patients. In clinical trials, the drug (marketed by Merck as Zetia) lowered levels of low-density lipoprotein or LDL, the so-called “bad cholesterol” associated with atherosclerosis, the thickening of blood vessels that can lead to stroke and heart attacks. Though LDL was also the target of the highly successful statin drugs, Zetia passed the FDA because it offered an alternative mechanism for reducing cholesterol levels, and soon was making billions of dollars a year for the pharmaceutical company. But as more and more people took the drug and more research was conducted, the scientific data did not match the marketing hype, with large clinical trials failing to find a protective effect against cardiac events and even finding in some cases that it made blood vessels thicker.

Sadly, the story of Zetia is not that unusual. In recent years, other drugs such as Vioxx and Redux have been come under fire when dangerous side effects or underwhelming clinical results became apparent after approval. These high-profile failures (and the inevitable ensuing lawsuits) have threatened to slow drug development, as pharmaceutical companies are understandably nervous about investing big money in a potential dud. Expensive new drugs that offer little to no improvement over pre-existing treatments also cause damage, by needlessly raising health care costs. So what changes can we make to the U.S. health care system to promote the creation of innovative new drugs worth their price tag?

Three authors, including G. Caleb Alexander of the University of Chicago Medical Center, proposed five not-so-easy fixes in a recent issue of Annals of Internal Medicine. Their strategy includes reforms of the FDA’s drug approval process, drug labels, and the payment strategy of insurance companies on the other. For drug companies that may not like the extra squeeze, incentives can be built into the system to sweeten the deal for developing more effective treatments and drugs for currently untreatable diseases. “Despite these challenges, the United States has a long history of successfully improving the safety and value of prescription drugs, and substantial progress can still be made,” the authors write.

1. Raise the Bar

One way to prevent surprises when new drugs are transferred from clinical trials to the real world is to require that higher standards are met before approval. Instead of just demonstrating the drug’s superiority to a placebo treatment, researchers could be required to prove that the new drug is better than the current standard of care. Clinical trials should also be designed to measure effects on clinical outcomes, such as atherosclerosis, rather than physiological measures, such as LDL.

2. Semi-Approval

For an FDA approval process that some already criticize as to slow, these additional requirements could further gum up the works. To allow time for this more thorough review, the authors suggest a more nuanced FDA approval, adding a new “conditional” approval stage where the drug could be available with strings attached. For instance, direct-to-consumer advertising could be restricted while more data is collected on the drug’s effects in a larger, more diverse population.

3. The Patent Carrot for the Regulatory Stick

For the pharmaceutical companies, all of the above is a nightmare that would extend the cost and time it takes to bring a new drug to market. As an olive branch, the paper suggests extending the patent exclusivity for new drugs that meet these most stringent standards, giving the pharmaceutical company more time to collect profits before generics are allowed to reach the market. One suggestion is to start the patent clock when the drug is approved, so that the FDA process does not eat up valuable months and years of exclusivity for the drug’s developer. Such a measure would also ease up the pressure on the regulators, reducing “the tension between the ticking clock of patent protection and drug safety,” the authors write.

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“A pox of this gout! or a gout of this pox! for the one or the other plays the rogue with my great toe.” - Falstaff, Henry IV

Gout was once called “the king of diseases and the disease of kings.” Thanks to that proximity to power, gout has been well documented through history, from the Egyptians to the Greeks to 17th century England, when physician Thomas Sydenham described an outbreak as “The night is passed in torture.” But today, gout has been democratized, afflicting roughly 6 million people in the United States and connected with obesity, heart disease, and alcohol abuse. Fortunately, treatments for gout have kept pace with its numbers, and in this week’s Journal of the American Medical Association, another option has been added to the physician’s arsenal against the rheumatic disorder.

The new treatment, pegloticase, has its origins in an unlikely place for a “royal” disease: an enzyme from the common swine. Unlike humans, most animals can avoid gout thanks to an enzyme called uricase that converts uric acid (high levels of which cause gout) to the harmless and excretable allantoin. Duke University chemists spent decades modifying pig uricase for therapeutic use in humans, adding a protective coating that can keep the enzyme active for days instead of hours. Perfected at last, the treatment showed positive results in its first two major clinical trials, run by researchers at the Medical Center.

“This represents the first effective therapy for a group of patients who previously had no options at all,” said the study’s senior author, Michael Becker, professor of medicine at the University of Chicago. “This is for patients with severe gout, including major disabilities and high levels of pain. Many of these people had dramatic responses within months…as well as reduced levels of pain and disability. The rapidity of these outcomes is unheard of.”

Gout is caused by the gradual accumulation of uric acid, either from over-production or inadequate removal. When levels exceed the saturation point, uric acid forms tiny urate crystals, like thousands of little needles, that deposit in the lining of joints and other tissues. The crystals can cause inflammation, swelling and intense pain, including painful swollen joint nodules known as tophi.

Many patients are treated with medications that block the synthesis of uric acid or help the kidneys remove it. But not everyone with gout finds relief from these medications, or can tolerate their side effects. Three percent of gout patients - about 120,000 to 180,000 Americans - have chronic, disabling disease with no effective therapy.

Those types of patients made up the two parallel trials of pegloticase, conducted at over 50 rheumatology clinics across North America. Patients in the treatment groups were given an intravenous infusion of pegloticase once every two weeks or once every month, and monitored for six months to see if their uric acid levels fell and their symptoms resolved. The results showed an interesting split: although uric acid levels dropped in all patients given the drug, only 42 percent (in the every-two-weeks group) sustained those decreased levels over the entire six months.

Still, helping two out of five patients without any other treatment option is a significant clinical achievement. And in those patients where the drug worked, the magnitude of relief was great, resolving at least one tophi and improving quality of life and physical function. The drug, brought to market under the name Krystexxa, is expected to cost about $60,000 a year.

“People are dramatically helped by the drug,” said rheumatologist John Sundy, director of the Duke Clinical Research Unit and lead author of the study. The drug’s response among patients who have failed common therapies is typically an “all-or-nothing result,” he added, “providing marked relief for those who benefit.”

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By John Easton

Let’s start with a statistic: almost 2,000 citations a year. One paper by Paul Meier, the Ralph and Mary Otis Isham Distinguished Service Professor emeritus of statistics, pharmacological and physiological sciences, medicine, and the college, has been cited more often, by a wide margin, than any other paper in the field. At last count it was the fifth most cited research paper of all time, in any field. With about 34,000 citations to date, Kaplan, E. L., and Meier, P. (1958), “Nonparametric Estimation from Incomplete Observations,” has been cited by another scientific publication about once, on average, for every day of Meier’s long life—he was born in 1924—and still counting.

Sadly, however, that ratio can only increase. Citation counting will continue, but the numbering of days stopped on Sunday, August 7th, when Professor Meier, a world-class statistician who made “extraordinary contributions to statistics and to society,” according to Columbia University - and everyone else - passed away peacefully at his Manhattan home.

The Kaplan-Meier estimator is used ubiquitously in medical studies to estimate and depict the fraction of patients living for a certain amount of time after treatment. This is not as simple as it sounds. Survival curves are complicated by the uncooperative way in which research subjects often behave. Some leave a study part of the way through. Others elect not to die before the study ends. These are known as “censored observations.” The Kaplan-Meier estimate is a simple way to compute the survival curve despite such troublesome behavior.

There was almost a Kaplan estimator and a Meier estimator. Each had submitted a separate manuscript to the Journal of the American Statistical Association, but the editor recommended that their papers be combined into one. It took them four years. “At one place he solved a problem that I couldn’t solve,” Meier later recalled in an interview [pdf]. “Other places I solved problems he couldn’t.” Finally published in 1958, it was only cited 25 times over the next ten years. Then, boosted by statisticians’ increased computing power, it caught on. It has since been applied to data from clinical trials of therapies for every disease from cancer to cardiology to concussion.

Friends and colleagues point out that this was only one of Meier’s fundamental contributions. He published many more studies, was a persistent and outspoken advocate for randomization in clinical studies, helped design some of the 20th Century’s most important clinical trials and trained many of the leaders in the field.

“Paul was a friend and colleague as well as one of the most influential statisticians of an important era,” recalled Stephen Stigler, the current chair of statistics at the University of Chicago. “He left an indelible mark on us, and through his research on the world’s clinic analytical practice. He will be missed and cannot be replaced.”

“I have been so fortunate and privileged to know this truly great, wonderful, helpful, kind man who was always so generous with his skills and wise advice,” said toxoplasmosis expert Rima McLeod, professor of ophthalmology and visual sciences at the University. “He is one of the founding fathers and giants of statistics in the past century. He was at the same time simply a modest, helpful, supportive and warm colleague who only let you know how special he was by the quality and content of what he said and wrote.”

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By John Easton

Salt is bad for you. According to a 2010 article in the New England Journal of Medicine, lowering dietary salt intake by 3 grams per day could “reduce the annual number of deaths from any cause by 44,000 to 92,000.”

Or maybe not. A 2011 meta-analysis of seven clinical studies of salt reduction, published this week in the American Journal of Hypertension, found “no strong evidence that salt reduction reduced all-cause mortality.” One of the seven studies showed that a low-sodium diet was associated with an increase in the risk of death for certain patients.

Studies of diet–eggs, caffeine and sugar; of screening tests–annual mammograms, PSA testing and lung scans for smokers; even topics as diverse as circumcision or drinking eight glasses of water a day, have all produced conflicting results. How can this happen? How often does this happen?

“We call them reversals,” said Adam Cifu, associate professor of medicine and co-author of a recent research letter on the phenomenon, published in the Archives of Internal Medicine. “Some new therapies are replacements,” he said. “They are better than what came before, as demonstrated by large, well designed, controlled studies.” Other new approaches arrive expecting to become replacements, but biology, complexity and, over time, better studies transform them into reversals.

“They make sense in the laboratory,” Cifu said. “Doctors are eager to try things that should work, based on what we understand about the biology. But the human body is complicated; things that made perfect sense in theory may not work in quite the same way in the clinic. We wanted to find out how often this happened.”

So Cifu and colleague Vinay Prasad, a former Pritzker student and now internal medicine resident at Northwestern, turned to the leading American medical publication, the New England Journal of Medicine. They focused on the 124 articles that appeared in 2009 involving investigation of a new medical practice or a practice already in adoption. Of those 124 articles, 16 could be characterized as a reversal. So 13 percent, one out of eight, contradicted an emerging or accepted medical practice.

The reversals included medical therapies such as tight control of blood sugars for patients in an intensive care unit, invasive procedures such as efforts to reopen clogged arteries for patients with chronic total artery occlusion, and predictive tests such as randomized prostate cancer screening.

One resounding reversal involved back-to-back studies in the August 6, 2009, issue that took a close look at vertebroplasty, a treatment for pain caused by compression fractures of the spine, a common problem for older women. The procedure, which had been widely used for more than a decade, involved injecting bone cement through a small hole in the back into a fractured vertebra. “We spent billions of dollars on this,” Cifu said. Several small early studies implied good results, but there had never been a blinded, placebo-controlled, randomized trial.

However, once NEJM published results from the first such trials, the party was over. One study found “no beneficial effect of vertebroplasty over a sham procedure at 1 week or at 1, 3, or 6 months.” The other reported that results for patients treated with vertebroplasty were “similar to the improvements in a control group.” An editorial in the same issue predicted the procedure, “virtually always considered to be successful,” would now be “considered no better than placebo.”

Cifu and colleagues developed a Why-We-Got-It-Wrong-Initially chart summarizing the reasons behind each reversal.

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Cancer used to be a black box, a disease that physicians could only monitor through surgical biopsies and indirect measures. But for the last thirty years, the use of computed tomography imaging, better known as CT scans, has allowed oncologists and cancer researchers to keep close watch on the growth or shrinkage of a tumor for many different types of cancer. A patient with a lung tumor, for example, can be scanned every few months in order to see whether their therapy is working - and if it’s not, doctors may choose to switch treatments. Clinical trials of new therapies for cancer also make use of CT scans, using the increase or decreased size of the tumor as a primary data point.

But for all the benefits of scans over surgeries to monitor tumor size, flaws remain for CT scans. A new study published this week in the Journal of Clinical Oncology shines a harsh light on one of the primary problems - the technology’s variability. Patients usually are given CT scans months apart, and trained radiologists measure the tumors to see whether they are growing or receding. But how much of those changes can be attributed to random error from the imperfect resolution of the scan or the breathing of the patient?

To test this baseline error, researchers from Memorial Sloan-Kettering Cancer Center got a little tricky. Instead of taking two scans from a patient months apart, they took two scans in quick succession, within 15 minutes. The scans were then handed off to experienced radiologists, who were told to measure the change in tumor size without knowing how much time had elapsed between the images. The results were sobering - despite the tumor being biologically identical between the two near-simultaneous scans, the radiologists found changes in size of 1mm or more in more than half of the samples and a 10 percent error range in either direction overall. Although the criteria for tumor progression is an increase in size of 20 percent or more, that 10 percent error could considerably distort the data when clinical and research decisions are made using normally-spaced scans.

The result doesn’t render CT scans obsolete, but offers new caution about the method’s shortcomings.

“It’s the sense of, ‘Really? Is this first happening now?’” Michael Maitland, assistant professor of medicine at the Medical Center, commented to Reuters Health about the study findings. “This is telling us scientifically how much noise is naturally there without any treatment or the cancer getting worse. It’s an important thing to do whenever you are going to use any kind of marker for a disease.”

In an accompanying editorial in the Journal of Clinical Oncology, Maitland went further, writing with his co-authors that it was time for oncologists to rely less upon CT scans alone and move toward integrating those images with other measures to create more precise monitoring technologies. As cancer edges toward more personalized treatment strategies, developing better diagnostic tools will become even more important, they argued.

“It is time to cast away familiar conventions and turn to better methods of evaluating malignant disease therapeutics,” they wrote. “It is time to replace these systems with more innovative, quantitative approaches that have the potential to define relationships between solid tumors, disease progression, and therapeutic outcomes in patients.”

Elsewhere…

It might have come out a few days late for the 4th of July, but Travis Carter’s study of the effects of seeing the American flag on political beliefs is still timely. If the Booth Business School researcher is right, we’ll all be slightly more Republican for at least the next 8 months. Ed Yong at Not Exactly Rocket Science did a great writeup that was featured on the Colbert Report this week (and also wrote up our own Neil Shubin’s study on the origin of limb genetic programs this week as well).

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The hepatitis C virus has always been an unusual disease. Largely symptom-free in its early stages, many people are unaware for many years that they have contracted the virus. But if left untreated, hepatitis C can eventually cause severe liver damage that may necessitate an organ transplant. Until recently, physicians have had only limited success in combating the hepatitis C virus, administering a lengthy combination of two drugs that completely cured less than half of the patients treated.

However, in recent months the forecast for curing hepatitis C patients became much sunnier. The near simultaneous FDA approval of not one, but two new therapies for the virus - called telaprevir and boceprevir - promises to dramatically improve the cure rate for the disease and prevent serious cases of liver cirrhosis and cancer. The two drugs are members of the same protease inhibitor class that has revolutionized HIV treatment, and adding one to the previous two hepatitis C therapies (forming what’s known as “triple therapy”) promises to increase cure rates to as high as 80 percent.

But new therapies bring loads of new questions and considerations for patients. At the University of Chicago Center for Liver Disease, which takes care of hundreds of hepatitis C patients, physicians Donald Jensen and Andrew Aronsohn organized a series of patient education sessions to address how the new therapies change the landscape of the disease. While many patients have been waiting years for the approval of telaprevir and boceprevir, choosing the right time to begin therapy is no simple decision. Because the therapy still takes between 24 and 48 weeks to complete, and must be closely monitored to make sure the protocol is successfully followed by the patient, hepatitis C clinics can only start treating so many patients at a time. In an editorial for the journal Hepatology, Jensen and Aronsohn explained why the University of Chicago has thus chosen to treat the sickest patients first, asking hepatitis C patients in the earlier, less severe stages of the infection to delay their therapy with the new agents.

To further spread information about these decisions, the basics of hepatitis C, and the impact of the new therapies, Jensen and Aronsohn agreed to film a series of videos for ScienceLife. Watch as the two physicians explain how the new therapies work, what patients can expect from the new treatment protocol, and why it is important for patients and their physician to choose the right time to start therapy.

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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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 mortality curves separate. (From Goodin et al. poster)

To conduct a clinical trial of a new drug, the researchers need to pick an ending: a place where the experiment will be stopped and the results between those taking the drug and those who haven’t can be compared. If the drug is a clear improvement, the trial will be stopped, and patients in the control group will be allowed to start taking the newly-proven treatment. Follow-up studies may then be difficult to conduct, particularly if the disease is too deadly or the patients are too hard to track.

So when almost every single member of a landmark study can be tracked down more than 20 years after its completion, that’s an impressive feat. Even more so when comparing the treatment and control groups two decades later reveals an unexpected, and very meaningful, long-term benefit. A new study, co-presented at two recent meetings by Anthony Reder, professor of neurology at the Medical Center, reveals that a multiple sclerosis drug first tested here 23 years ago continues to show benefits in patients on perhaps the most important outcome of all: mortality.

Interferon-β-1b was the first drug proven effective in slowing the progression of MS, based on a trial of 372 patients conducted at the University of Chicago and 10 other centers from 1988 to 1993. When the FDA approved the drug in 1993, its effects on quality of life were emphasized by Barry Arnason, professor of neurology and one of the study’s lead investigators, who told the New York Times that “People are going to stay on their feet longer, work longer and be happier.”

The researchers could not have anticipated that the drug might also help MS patients live longer as well. But when follow-up data was collected 16 years after the trial’s completion, a promising hint emerged. Researchers successfully re-established contact with 88 percent of the original subject pool for a paper in the journal Neurology, and confirmed the long-term safety of interferon treatment - their primary goal. But a secondary finding also attracted interest. Of the 328 patients contacted from the original trial, 35 had died, but only 6 of those were from the original high-dose interferon group, vs. 20 from the control group.

Because patients in the control group were also placed on interferon treatment after completion of the trial, the result suggested that starting interferon earlier had long-term benefits on mortality. But to confirm the effect, the researchers had to find even more patients from the original study, alive or deceased. For the 21-year follow-up, they expanded the coverage to an astonishing 98.4 percent of the original subject pool, lacking information on only 6 of the original patients.

Fortunately, the larger dataset confirmed the earlier promising hints on mortality. As presented at the American Academy of Neurology Meeting this month by Reder and neurologist Douglas Goodin of UCSF, patients who received interferon during the 1988-1993 trial were less likely to have died at the time of the follow-up. Of 81 patients who had passed away in the 21 years since the trial, nearly half were originally in the placebo group, meaning they had started interferon treatment roughly 4 years later than those enrolled in the two treatment groups. Remarkably, even those who had received interferon in the pivotal trial weren’t started on the drug until an average of 8 years after MS symptoms first appeared, much later than current clinical standards, Reder said.

“Even stacking the deck against us by relatively late treatment, and accounting for a follow-up period where all of the people were on the best possible medicine for them, we still see this huge difference,” Reder said. “We think this means there’s a very important survival effect of interferons.”

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In physics, there’s nothing better than an unexpected result. Wednesday, Fermilab scientists unveiled the graph at left and caused figurative rioting in the streets of the physics community, confirming months of rumors about an exciting new result from the suburban Chicago facility (You can watch video of the presentation here). It’s a big score in the final days of Fermilab’s Tevatron accelerator, which is due to close later this year due to budget cuts and the ascendancy of the more powerful CERN Large Hadron Collider in Switzerland.

The buzzworthy peak was the result of collision experiments where Fermilab scientists expected to see a W boson and two quarks, elementary particles that are part of the Standard Model of physics. But the experiments produced something additional, something unexpected, something unusual: a bump. Particle physicists spend their whole life chasing bumps, as Sean Carroll of Fermilab explains at his Discover Magazine blog, because they are “often a signature of a new particle that has been produced and then quickly decayed.” The anomaly could thus be a previously undiscovered particle that is not predicted by the Standard Model (apparently it is too large to be the elusive Higgs boson), forcing a re-write of the core theory of modern physics. Even if it’s not a new particle, some say an incorrect prediction like this one could mean that some of the rules of the Standard Model may need to be tweaked.

But despite the excitement, caution still reigns - as Dennis Overbye wrote in the New York Times, “The key phrase, everyone agrees, is ‘if it holds up.’” The chance that it is just a statistical anomaly is less than 1 in 1375, the researchers said. With that kind of data, biologists (whose 1 in 20 standards were lampooned effectively by the science comic xkcd this week) would already be popping champagne, but it’s not good enough for physicists - past findings of that strength have disappeared with further scrutiny. If additional experiments still being analyzed push the chance of error to 1 in a million, the true celebration will begin, and the finding could be the most important piece of new physics in decades.

Scientific Shutdown

Fortunately, that analysis will continue even in the face of a threatened government shutdown, the Fermilab website assures. But if a budget agreement isn’t reached by midnight tonight, business won’t continue as usual for many scientists, beginning with the 6,000 employees of the National Institutes of Health. As for extramural research that relies upon federal dollars, most ongoing clinical trials will be unperturbed, experts said. But Johns Hopkins researchers said that no new clinical trials will be able to start during the shutdown, and the Medical Center’s Richard Schilsky told MedPageToday that he’s concerned about obtaining experimental drugs from the National Cancer Institute.

“The biggest issue for us would be studies of investigational drugs being supplied by the National Cancer Institute,” he said in an email. “Many times we have to order drugs for each unique patient to be treated, and if NCI shuts down and can’t ship the drug, then we can’t treat the patient!”

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Reading The Emperor of All Maladies, Siddhartha Mukherjee’s “biography of cancer” from last year, one is struck by both the long and short history of cancer. Descriptions of breast cancer can be found as long ago as an Egyptian papyrus dated to 2500 BC and ancient Greek histories, and tumors have been found in thousand-year-old mummified remains from Peru. But the idea of cancer as a treatable disease is barely a hundred years old, and as recently as the 1940’s, clinicians could do little more than help patients die from the disease as comfortably as possible. Despite these deep historical roots, Mukherjee chooses to start his book in 1947, with Sidney Farber’s first experiments on chemotherapy for children with leukemia.

From there, the pace of the “war on cancer” (though not known by that phrase until 1971’s National Cancer Act) accelerates rapidly, as chemotherapy, radiation and surgical protocols were improved through scientific inquiry. Progress in understanding and treating cancer no doubt seemed incremental as it was happening, and even today some still question its overall success. But Mukherjee’s skillful portrayal presents an astonishing difference in the experience of cancer patients only 50 years apart - from being hidden in out-of-the way wards because of the hopelessness of their condition, to the ultra-modern cancer centers of today offering targeted treatments that offer the promise of a cure, if not yet a certainty.

But stumbling blocks still exist in the scientific progress against cancer. One place where reinforcements are desperately needed is at the level of clinical cancer trials, where the true benefits of laboratory discoveries are put to the test in a human population. While there is no shortage of ideas for new cancer therapies, clinical trials have struggled due to insufficient accrual of patients. Though 25,000 to 30,000 patients are enrolled in cancer trials each year, they only represent 3 to 5 percent of all U.S. adult cancer patients,  Richard Schilsky, professor of medicine and chief of hematology/oncology, wrote in a commentary for Science Translational Medicine last week.

“Despite various attempts to remedy the accrual problem, such as awareness campaigns, establishment of clinical trial registries, and the development of search engines to match patients to trials, annual enrollment on cooperative group clinical trials has remained essentially unchanged throughout the past decade,” he writes. As a result, “up to 40% of cooperative group phase III trials have failed to complete accrual and closed without achieving study endpoints, wasting the contribution of those patients willing to enroll in the trial.”

There are plenty of barriers against getting cancer patients into appropriate trials, Schilsky says. Many are institutional - physicians outside of the academic world may not have dedicated research staffs than can help coordinate patients, deal with regulations and insurance issues, and fill out the extensive paperwork. To circumvent these issues, some doctors would rather write off-label prescriptions for drugs being tested in a clinical trial, getting the potential benefits of the drug without the logistical commitments. On the other side, patients may not be aware of the trials available to them, or may misunderstand the purpose of a clinical trial.

The new era of molecular medicine could raise some of these obstacles even higher or knock them down, Schilsky writes. In 2001, the drug Gleevec ushered in the age of smarter drugs that directly interfere with the cause of the disease, rather than general features of tumor growth. Testing these types of drugs requires new types of trials, with more biospecimens (blood, tumor tissue, DNA) collected from patients and tighter rules about who is eligible for the experiments. Classifying broad cancers into more specific subtypes may eventually improve treatment effectiveness, but in the short term could make testing those treatments even more difficult.

“The challenge is that many patients may need to be screened if the biomarker used for patient selection is of low prevalence in the tumor type under study,” Schilsky writes.

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Sen. Dick Durbin tours Argonne National Laboratory with Rick Stevens, Professor of Computer Science (photo courtesy of Argonne)

In Washington, the fight over budget cuts is well underway, as a Republican majority in the House and a Democratic majority in the Senate tussle over the best way to reduce a multi-trillion dollar federal deficit. The first bill of the new House, H.R.1, set federal appropriations for the rest of fiscal year 2011 (ending in September) and snipped $61 billion from the budget, predominantly from discretionary domestic spending. One target of those cuts would be the National Institutes of Health budget, which would lose roughly $1.6 billion of its $32 billion budget for funding scientific research in the United States.

As you might expect, this news was not welcomed by Chicago-area researchers, who turned up in lab coats to support a news conference by Sen. Dick Durbin last Sunday at Northwestern University’s downtown campus. Durbin vowed to fight against the cuts as H.R.1 is discussed in the Senate, saying that interrupting the funding would slow progress toward new treatments for diseases such as AIDS, diabetes, and cancer. (video here)

“When you put these research projects on hold, you can’t ask the laboratory mice to take a nap,” Durbin said. “You can’t ask the cultures to stop growing - we’ll get back to you at the end of the fiscal year. And you can’t expect the professional researchers, the men and women who have dedicated their lives to medical research, to have certainty that next year they’ll have a job.”

Researchers from each of the major Chicago academic hospitals appeared at the conference and talked about how the proposed budget cuts could harm their own projects. Michelle Le Beau, director of the University of Chicago Comprehensive Cancer Center, discussed the biomedical research underway at UChicago thanks to the nearly $300 million in NIH funding received this year and last. Le Beau focused in on her own research examining therapy-related acute myeloid leukemia - a “very cruel and ironic” cancer caused by the chemotherapy and radiation treatment of a prior tumor. Any job losses that follow from NIH cuts could break up the expert team she has formed to study causes and treatment of the disease, she said.

“A lapse in funding will result in dismantling our highly specialized research team, and this leads to a loss of capability, because it takes years to assemble these teams again,” Le Beau said. “These are individuals who have trained for years to apply their extraordinarily unique skills. They have families to support and bills to pay.”

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

It’s great to have a treatment that’s proven to work in a difficult psychiatric condition such as anorexia nervosa. It’s even better to have two treatments for such a disorder. But having multiple options also creates a quandary for psychiatrists: with a new patient, which treatment do you try first? Creatures of habit like the rest of us, many doctors will simply stick with the method they know best until given convincing evidence that it’s worth switching gears. To be the new treatment of choice, a method must beat out the current champion in a head-to-head battle.

One such comparison, conducted by researchers at the University of Chicago Medical Center and Stanford University, was published yesterday afternoon in the Archives of General Psychiatry. The trial compared the most common form of treatment for adolescents with anorexia, known as adolescent-focused therapy (AFT), with the newer, family-based treatment (FBT), also sometimes known as the Maudsley Approach. The latter name comes from the Maudsley Hospital in London, where Daniel Le Grange, now director of the Eating Disorders Clinic at the University of Chicago, helped develop a new approach to bringing anorexic teens back to healthy weight and eating habits.

Under adolescent-focused therapy, the therapist works directly with the patient on a one-to-one basis, emphasizing the importance of weight gain and helping them accept personal responsibility for healthy eating. Family-based treatment, as you might expect from the name, does more to incorporate the parents into that process, equipping the patient’s mother and father with the tools to encourage healthy eating at home. By doing so, the therapist hopes to avoid hospitalizing the patient while permanently adjusting the home environment, removing factors that could lead to relapse after therapy is completed.

“No one is more available to care for the kids than the parents are; no one would put the time aside in the way that parents would, and no one loves their kids more than parents do,” Le Grange told NPR’s Morning Edition (where you can also hear the perspective of one patient’s mother on family-based treatment).

The two therapies had been compared previously, but in smaller studies with only two or three dozen patients. True convincing evidence requires a randomized trial, with enough patients for the statistics to make a strong case for one of the treatments. So, combining forces between Chicago and Stanford, Le Grange and his collaborator, James Lock at Stanford, were able to gather 120 patients with anorexia nervosa (with an average age of 14-1/2) for the study.

Split evenly between FBT and AFT, the patients were followed for a year of therapy and another year of follow-up. At the end of treatment, 42 percent of those enrolled in FBT showed full remission back to at least 95 percent of expected body weight, compared to only 23 percent of those enrolled in AFT. While that comparison fell just short of statistical significance, with a p-value of .055, Le Grange said that the higher standards used in the study spoke to the effectiveness of FBT.

“We used the higher yardstick for remission of 95 percent of body weight, which we felt was clinically more appropriate,” said Le Grange, a professor of psychiatry and behavioral neuroscience.

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