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!

A visit to any casino will quickly demonstrate how vices clump together. At any hour of the day or night, many of the customers sitting intently in front of a slot machine will also be smoking cigarettes or drinking a cocktail. Sadly, addictions to these pursuits also tend to go hand in hand, with higher rates of compulsive gambling observed in people addicted to drugs such as cocaine and alcohol. Furthermore, when people perform gambling-like tasks while their brain is scanned by an MRI machine, the games activate areas of the brain also stimulated by drugs of abuse - perhaps accounting for the addiction-like behavior of gamblers.

“If you’ve ever been to a casino, and you watch people using slot machines, you’ll surely have noticed the sense of compulsion to put the next coin in, even though you get no money back most of the time,” said Paul Vezina, professor of psychiatry and behavioral neuroscience at the University of Chicago.

But does one bad habit truly lead to the other? In a recent paper for the journal Behavioural Brain Research, a team from Vezina’s laboratory offers evidence that the unpredictability crucial to gambling’s appeal can cross over to enhance the effects of abused drugs. By adapting self-administration, a common tool used to model drug-taking in animal research, to partially replicate the random pay-off of a slot machine, graduate student Bryan Singer was able to test whether gambling-like behavior influences a rat’s subsequent response to the drug amphetamine. The result suggests that gambling may have properties similar to a “gateway drug,” as an activity that can increase the abusive potential of drugs.

First of all, how do you simulate the casino experience for a rat? Self-administration - where the animal presses a lever to receive a food or drug reward - is fairly similar to a slot machine to begin with. In a self-administration protocol, the researcher sets the number of lever presses required before the reward is given. A “fixed ratio” of 5 means that the rat would have to hit the lever five times before receiving a food pellet or rewarding hit of cocaine. But with a “variable ratio” setup, unpredictability is introduced into the process. If the variable ratio is set to an average of 5, anywhere from 1 to 10 presses might be required to produce reward, a figure that changes every time like the random number generator of a slot machine. So while the rat does not have anything at stake other than the physical work it takes to hit the lever, it never knows when it will hit the “jackpot.”

“One of the main differences is that for a slot machine there’s a good chance you’re going to lose money, but here there’s little negative aspect,” Singer said. “It’s like a very loose slot machine.”

In this experiment, Singer and co-author John Scott-Railton used the non-caloric sweetener saccharine as a reward - a sweet treat that rats will work to acquire without ever getting full or intoxicated. For 55 days, half of the rats worked for saccharine under fixed ratio conditions and half worked under the variable ratio setup. Then, after a two week break, each rat was given a small dose of amphetamine, and researchers measured their activity as the dosed rats ran around their cage.

Even though the rats in each group received the same amount of saccharine and did the same amount of work during their lever-pressing careers, those exposed to the random rules of the variable ratio exhibited a stronger response to amphetamine. The result suggests that unpredictable rewards may prime the same brain areas hijacked by drugs of abuse, producing a stronger behavioral response - known in the field as sensitization - even upon first exposure to a stimulant drug.

“What this paper is showing is that unpredictable conditions may cause sensitization,” Vezina said. “There are activities that may play just as important a gateway role as drugs, and gambling may be one of them.”

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Medical school isn’t cheap. Today, medical students graduate with an average debt over $155,000, and the need to pay off those mortgage-sized loans drives many a young doctor away from more modestly compensated but sorely needed fields such as primary care and family medicine. To alleviate this financial pressure, many organizations have started scholarships to help with the med school tuition bill, rewarding scholastic achievements and commitments to work in underserved populations. The American Medical Association’s Physicians of Tomorrow program is one such effort, and this week’s announcement of the 2011 recipients [pdf] carried a heavy Pritzker School of Medicine presence.

Two of the 18 (11 percent, but who’s counting) fourth-year medical students receiving the $10,000 scholarship were from the University of Chicago’s medical school. Laura Blinkhorn (left) and Maggie Moore (right) are the two very impressive Pritzker students among the recipients, each with very impressive biographies already built in their young careers. Blinkhorn has done work with South Side neighborhoods as part of the Pritzker Summer Service Partnership, works with the Washington Park Free Children’s Clinic, and is planning to spend 3 months of the next year doing a clinical rotation in the African country of Gabon. Moore volunteered at the Maria Shelter Clinic for Women and Children and the South Side “Girls on the Run” program, and somehow finds time to write poetry about her medical experiences. Because of poems such as “Cadaver Memorial” and a collection called “A Third Year’s Life in Lyrics,” Moore was given the Johnson F. Hammond, MD Scholarships supporting medical journalism by the AMA. Congrats!

New Furniture for Molecular Engineering

When you are building a new house, you’re gonna need some furniture. The same thing goes for building a new research institute - before you can fill it with people, you need somewhere for them to sit. The University of Chicago’s Institute for Molecular Engineering, which was born in December and acquired a leader in March, has this week announced four named professorships made possible by anonymous donations. The funded positions give the institute the power to recruit prominent researchers to help realize the institute’s unique vision blending biology, chemistry, and physics.

“The big job in front of us is to bring together people with expertise in broadly applicable areas of enabling technology, such as synthesis of new materials, biological engineering, new ways of doing computing and quantum information science,” said Matthew Tirrell, the founding Pritzker Director of the Institute for Molecular Engineering and senior scientist at Argonne.

Elsewhere…

The San Diego Union-Tribune Keith Darcé wrote an excellent overview of the Earth Microbiome Project, the global study of the world’s bacterial populations that has previously been featured on the blog. Our own Jack Gilbert is featured (he mentions their current project swabbing bacteria from the animals of the San Diego Zoo), and an interesting hunt for bacteria able to survive in high-salt conditions is also explained.

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One of the sectors closely monitoring the debt debate in Washington is the medical world, where hospitals, physicians, and patients anxiously await the final agreement on cuts to Medicare and Medicaid. Of particular concern to academic medical centers [pdf] are proposed cuts to graduate medical education, funding used to pay the salary of residents and fellows who are both training as physicians and specialists and working on the front lines of patient care. In a time when a patient’s wait time to see a specialist grows longer and longer, squeezing the bottleneck of physicians-in-training even tighter could have long-term consequences.

This week, the Medical Center’s executive vice president for medical affairs and dean Kenneth Polonsky took to the newspapers to argue against these damaging cuts. In an op-ed letter published by the Chicago Tribune, he expressed concern that the proposed cuts would “would reduce access to doctors, multiply waiting times and do lasting harm to patients in Illinois and nationwide.”

No one questions the need to rein in spending on health care or the obligation of hospitals to do their part. But we need to maintain a high level of patient care, and to make certain that our country has enough physicians in the future. Policymakers in Washington must maintain their support for graduate medical education and find more equitable ways to distribute the budget-cut burden.

Elsewhere…

Speaking of Washington and health care policy, without the Patient Protection and Affordable Care Act, 63-year-old Glenn Bovard of Valparaiso would not have been able to receive life-saving gift this past Father’s Day: a new heart. The Post-Tribune profiled Bovard’s story and surgery, performed by the Medical Center’s Valluvan Jeevanadam and Jai Raman. “The surgery was a cakewalk compared to the heart attack,” Bovard told the paper.

As many as one-third of patients with epilepsy cannot control their seizures with medication. Local newsmagazine Chicago Tonight profiles efforts by Wim van Drongelen, technical and research director of our pediatric epilepsy center, to develop new ways of helping these patients by modeling how seizures begin and spread in the human brain.

At the end of a long, difficult week, many people like to unwind on a Friday evening with a drink? But does alcohol relieve stress, or prolong it? A new study by Emma Childs of the University of Chicago Behavioral Pharmacology Laboratory and written up by the Gannett News Service suggests a double-edged sword - stress reduces the positive effects of alcohol, while a drink may extend the tense feelings produced by a stressful event.

A cautionary tale about when newspapers twist the words of scientists for sensationalist ends - did paleozoologist Darren Naish really say that the Loch Ness Monster was “more fact than fiction?”

Evolution isn’t only a process that happened in the distant past. Carl Zimmer’s wonderful cover story in the Science Times this week follows New York evolutionary biologists as they hunt for signs of urban evolution in progress for mice, fish, ants, and other city-dwelling critters.

Every new experience leaves a mark on our brain, from a fleeting burst of electricity and neurotransmitters to a longer-lasting architectural shift. When we meet a new person, learn a new fact, or visit a new place, connections in our brains strengthen and weaken accordingly to store a memory for minutes, days, months, or years. But there are other ways to produce long-term changes in brain structures, forming “memories” that may drive behavior in subconscious ways. A recent strain of research has discovered that the drugs humans use - from alcohol to cocaine to heroin - all produce long-lasting changes in the brain, hijacking the mechanisms of memory with sometimes dangerous results.

The laboratory of Daniel McGehee, a neuroscientist and associate professor in the Department of Anesthesia & Critical Care, studies how one of the world’s most popular drugs, nicotine, can dramatically alter regions of the brain involved in reward. Normally, these brain areas (which include the ventral tegmental area and nucleus accumbens) help motivate animals to pursue natural rewards such as food and sex that are necessary for life and reproduction. But for centuries, humans have been drawn to substances that produce those same rewarding sensations despite being inessential for life - cigarettes, alcoholic drinks, or harder stuff. When these rewarding drugs are used often enough, people can become dependent or addictive upon their effects, suggesting that their brain reward system has been somehow re-tuned to pursue the drug despite significant personal cost.

In 2000 and 2002, McGehee and former post-doc Huibert Mansvelder published two papers that characterized how nicotine can produce memory-like long-term changes in the ventral tegmental area (VTA). The excitability of neurons that release the neurotransmitter dopamine is known to be related to reward - loosely put, when the neurons are more active and release more dopamine in the nucleus accumbens, the feeling of reward is stronger. McGehee and Mansvelder took slices of rat brain that can be kept “alive” in solution for a few hours after dissection, and measured the activity of dopamine neurons before and after exposing the slices to nicotine. The effects mirrored a well-studied process of memory formation called long-term potentiation (LTP) - the excitatory drive to dopamine neurons increased, while the inhibitory drive decreased, producing a lasting increase, a sort of nicotine-induced “memory” in the reward system.

“When we’re learning things consciously, we repeat things, and that apparently reinforces the memories,” McGehee said. “We believe that cells are working in a similar way: the stronger the activation, the more repetition of excitation of that synapse, the stronger it becomes. That is a sort of memory, as it lasts for extended periods of time.”

In a new paper, published last week in The Journal of Neuroscience, McGehee and post-doc Danyan Mao looked at the longer-term effects of nicotine in VTA. In the Mansvelder experiments, changes in dopamine neuron excitability was observed in the minutes following nicotine exposure. In Mao’s experiments, she exposed the slices to the amount of nicotine the brain encounters after a single cigarette, then waited as much as 5 hours after drug to measure the electrical activity of the neurons. Once again, VTA dopamine neurons were more excitable, even long after the nicotine was removed. But the way those long-term changes are formed were found to be subtly different in Mao’s study, bringing the effects of nicotine in line with another commonly-abused drug.

“We found that nicotine and cocaine employ similar mechanisms to induce synaptic plasticity in dopamine neurons in VTA,” Mao said.

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Despite what beer commercials tell you, not everyone responds to alcohol in the same way. For some people, an alcoholic drink is a party-starter, increasing energy and sociability. For others, a drink can be a party-ender, producing feelings of fatigue and sluggishness. In pharmacological terms, alcohol is a mixed stimulant/depressant, able to produce a wide range of behavioral effects. But does an individual’s place on this spectrum of alcohol response predict more than their night on the town? Can it say something about their future potential to binge drink, or abuse alcohol in other ways?

Classically, psychiatrists have linked an individual’s alcohol response to their potential for abuse through one simple word: tolerance. According to the low-level response theory,  reduced “intoxicating” effects of alcohol were associated with heavier drinking, as individuals have fewer internal cues warning them to stop. But the experiments that informed the low-level response theory focused on the depressant effects of alcohol, measuring predominantly sedation in test subjects. What about the positive and rewarding effects that inspire some people to drink in the first place?

“What is intoxication? It’s really bi-modal,” said Andrea King, professor of psychiatry and behavioral neuroscience at the Medical Center. “Some people can think intoxication is great - you’re drunk, it’s fun - while others think of it as something bad, that it’s a toxic reaction.”

King studied both of those alcohol responses in a 2002 study, giving heavy and light drinkers a disguised drink in a laboratory and asking the how it made them feel on a variety of measures. The study found that heavy drinkers were indeed more likely to report positive and rewarding effects of alcohol, even when they didn’t know it was alcohol they were drinking. From that small study, King and her team sought to both expand their subject pool and follow participants for years to see how their acute responses in the lab tests might predict their future drinking behavior.

The first data from that epic undertaking - a two-year followup of nearly 200 subjects aged 21 to 35 - was published yesterday in Archives of General Psychiatry. True to King’s hypothesis, an individual’s response to a mystery drink was predictive of how their drinking behavior evolved over the following two years, with both stimulant and sedative effects playing a role. While some subjects who were heavy drinkers at the time of the original experiments curtailed their binge drinking episodes, others demonstrated an “exacerbating” trajectory, binge drinking more frequently - up to half of the days in a month.

The path a subject followed could be foretold by their acute response to alcohol in the lab. Subjects with both higher sensitivity to the rewarding effects of alcohol and lower sensitivity to its depressant effects were found to have the most alcohol problems in the follow-up period. Those subjects drank more and more often, increased the frequency of binge drinking, suffered more alcohol-related consequences, and were more likely to qualify for a diagnosis of an alcohol-use disorder.

“The results change our thinking about how alcohol responses affect the development of an alcohol-use disorder,” King said. “It’s not just overall tolerance, but also sensitivity to alcohol’s euphoric effects that increases risk for excessive drinking.”

This new theory, dubbed a “modified differentiator theory” in King’s paper, could be a game-changer for how substance abuse experts identify people at-risk for alcohol problems.  Those who respond very positively to an alcoholic drink might be warned early on that they are at elevated risk for drinking problems.

“If we know more about who’s going to become a problem drinker, we may be able to prevent future escalations and intervene earlier, before development of severe alcoholism,” King said. “The stimulant-type responder could learn that while such a response pattern may not be their fault, it could put them at risk for longer-term problems and consequences.”

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Like the rest of campus, the MacLean Center for Clinical Medical Ethics seminar series is on spring break, resuming in early April with a talk from provocative economist Richard Epstein. So now’s a good chance to get caught up on the previous quarter’s seminars, covering topics under the umbrella of health disparities from the biological factors of breast cancer to the relationship between crime and public health to some of the exciting projects from the Urban Health Initiative. Hopefully, the ScienceLife coverage has kept interested readers informed about the valuable contents of this unique seminar series, but if you prefer a more visual experience, the MacLean Center website has posted several of the lectures in video form. Here’s a recap of the Winter Quarter sessions that are currently available for viewing.

Eliminating Global Disparities in Breast Cancer - Olufunmilayo Olopade Jim Fackenthal, University of Chicago

Unfortunately, Dr. Olopade was unable to deliver her talk due to a last-minute conflict, but Jim Fackenthal, research associate assistant professor in her laboratory, was able to provide emergency relief. The disparity in the survival rates of white women and black women in the United States with breast cancer remains wide, and while some of this gap can be explained by socioeconomic factors, biology also plays a role. Fackenthal talks about the evidence for more aggressive and harder to treat forms of breast cancer in women of West African origin here and abroad. The group’s research projects span from laboratory experiments on genetics and epigenetics to blood testing and screening in Nigeria.

Births to Arab-American Women Before and After 9/11: Evidence of Stress Effects - Diane Lauderdale, University of Chicago

The terrorist attacks of September 11, 2001 were stressful for all Americans, but possibly most challenging for Arab-Americans who experienced discrimination in the wake of the events. Lauderdale, a professor of epidemiology, wanted to look at whether one could measure a negative health impact of this discrete period of stress, choosing premature or underweight births as a health outcome potentially sensitive to discrimination. It wasn’t an easy task, as Lauderdale and her collaborators first had to develop an algorithm to find names in California’s birth registry that are likely of Arab origin. But the results of the study were striking, as Lauderdale was able to measure a spike in babies born underweight to Arab-American mothers in the months after 9/11, without any significant changes among other ethnicities.

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Photo by "BankingBum" - Wikimedia Commons

The leading cause of death for American black men between the ages of 15 and 34 isn’t cancer, AIDS, heart disease, or even accidents. It’s homicide, which accounted for more than half of the deaths of black 15 to 24-year-olds and more than a third of those aged 25 to 34. In Chicago, African-American males aged 15-24 are 10 times more likely to be killed in a homicide than white males, and in 2004, more African-Americans died from homicide than diabetes, HIV, or stroke. Genetic predisposition, access to health care, diet and exercise - all pale in comparison to bullets and knives.

Those numbers clearly argue that any discussion of health disparities between white and black populations in the United States can’t be limited to disease, said Harold Pollack in his MacLean Center for Clinical Medical Ethics seminar in late January. Urban, minority populations bear the brunt of the consequences of crime, he demonstrated, including not only homicides but also non-fatal injuries, incarcerations, economic damage, and stress. So while a project like the University of Chicago Crime Lab, for which Pollack serves as co-director, is rooted in the social sciences, the success or failure of its mission will surely have an impact upon medicine and community health.

“If you actually count up the number of dead bodies and in particular the number of life-years lost, homicide is a significant public health threat and it requires a systematic, determined response,” Pollack said.

The most shocking graph Pollack showed during his talk had nothing to do with cancer rates or disease mortality, but instead with incarceration. While the proportion of Americans behind bars remained stable from 1920 to 1970 at roughly 1 in 1,000, from there the numbers took an upward spike to make the climate change “hockey stick” graph jealous, increasing fivefold to today’s rate. As the numbers of jailed Americans skyrocketed, the prison population also became significantly less white, Pollack said, with the white incarcerated population dropping from 60 percent to 30 percent of the whole.

The “incarceration epidemic” causes significant public health ripples, both direct (through violence, HIV transmission, and drug addiction) and indirect. Disparities of incarceration have strained relations between minority communities and police, Pollack argued, making crime prevention in dangerous neighborhoods more difficult. Hiring biases against applicants with criminal records make it hard for convicted felons to find jobs (not to mention health insurance) after their release, steering them back toward illegal activity. For those jailed as juveniles, the lost time in school only intensifies the struggle to find legit work.

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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.

Thanks to its association with the Thanksgiving turkey, tryptophan has become probably the most popular amino acid. Whether it’s being blamed for the strong post-meal desire for a nap or being rhymed with “gravy in the pan” in a dancey clothing store commercial, tryptophan is the envy of its 19 peers in the standard amino acid family. But like most scientific crossover stories, public misperception has given turkey’s tryptophan something of a bad rap as a kind of natural sleeping pill - or a convenient excuse to not do dishes.

In fact, research has shown that turkey has no more tryptophan than any other poultry or ground beef; perhaps people should pull out the old “tryptophan” excuse the next time they eat a burger, as well. Simply eating a bunch of carbohydrates, such as the rolls, potatoes, and stuffing on the table next to the turkey, can spike a person’s tryptophan and insulin. The latter, a hormone best known for causing cells to absorb blood sugar, also causes the absorption of amino acids - except tryptophan, which crosses over into the brain. There, it is turned into the neurotransmitters serotonin and melatonin, which, yes, cause sleepiness, but also have a number of other interesting behavioral effects.

The powers of tryptophan are perhaps best depicted by what happens to a person when it’s not there. Tryptophan depletion is a frequently-used tool in psychiatry research, mostly as a shortcut to reducing the levels of serotonin in the brain. Because serotonin has been implicated in depression (many anti-depressant drugs are designed to increase brain serotonin) and impulsivity, some interesting things happen when you remove its key amino acid ingredient from a person’s diet.

In 2009, the laboratory of Emil Coccaro, chair of psychiatry at the University of Chicago Medical Center, used tyrptophan depletion to study an element of intermittent explosive disorder (IED). People with IED tend to have violent temper tantrums that do harm to themselves and others, and show signs of abnormal serotonin signaling, so Coccaro’s group, led by Michael McCloskey, studied the effects of tryptophan depletion in this group. Subjects with IED and controls without the disorder were given a tryptophan-depleting drink: a chocolate-flavored liquid that contained all the other dietary amino acids. Test subjects were then given a test where the punishment for failure was an electric shock; participants were allowed to choose the intensity of their shock.

Independent of the pre-test drink, IED subjects chose a stronger shock punishment than control subjects. But after quaffing the trytophan depletion drink, both IED and control subjects were more likely to choose a higher shock than when they consumed a placebo drink. That result suggests that lower one’s tryptophan, and by extension their serontonin, increases self-aggression and self-injury.

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The common wisdom about kicking an addiction is to “isolate and conquer.” People trying to give up smoking, or coffee, or something more serious, are usually advised to stay away from reminders of their drug, such as other people smoking, the smell of coffee, or other cues that might remind them of their habit. Taken to its extreme, this isolation policy is the backbone of inpatient drug treatment programs, which remove an addict from their environment and away from addiction “triggers” for 30 days or more. At the hospital, addicts can safely pass through withdrawal symptoms, receive psychiatric care, and return to society equipped to resist the siren call of their vice.

However, research in animals throws a wrench into that theory of addiction treatment. In animals taught to hit a lever to receive addictive substances such as cocaine, heroin, or sucrose, an extended period of abstinence away from drug-related cues produces an unintended effect. Rather than decreasing the animals’ response to the cues (which in the world of a rat’s cage is usually a light or a sound rather than an ashtray or a syringe), longer periods of abstinence inspire a more robust and energetic “relapse” of lever-pressing.

This “incubation effect” suggests that the longer addicts stay away from their drug, the more likely they are to succumb to a relapse when they see or smell a drug-related trigger. But that idea had not been translated from rats to humans until an experiment performed by Gillinder Bedi and colleagues in the laboratory of Harriet de Wit, professor of psychiatry at the University of Chicago Medical Center. Published last month in the journal Biological Psychiatry, the experiment shows the first evidence that incubation of drug cues also occurs in humans. Further, their results suggest that current treatments for addiction may miss, or even run counter to, an important cause of relapse.

“Many factors contribute to relapse,” de Wit said. “One is the presence of withdrawal symptoms, the other is just the immediate difficulty of removing a habit that you had. But there might be this other factor, incubation, that grows over time without dissipating, at least for weeks or perhaps months.”

In Bedi’s experiment, cigarette smokers were paid $30 a day to abstain from smoking for as long as 35 days. As testament to the allure of nicotine, only half of the subjects recruited for the study reached their smoke-free target despite the financial rewards, de Wit said. The participants who did successfully abstain until their goal (7, 14, or 35 days) returned to the lab where they were exposed to either smoking-related cues (pictures of people smoking, lit cigarettes, ashtrays, etc.) or neutral cues or a matched show of neutral, non-smoking cues. To enhance the sensory experience, subjects held a lit cigarette while viewing the smoking cues or a pencil during the neutral session. Before and after the cues, subjects completed surveys to report how strongly they craved cigarettes.

Before the slide show sessions, participants reported expected, positive results of quitting: withdrawal symptoms and craving decreased with the more days since their last cigarette. But after viewing the parade of cigarette-related images, the opposite effect was observed. Subjects assigned to the group that abstained from smoking for a longer period of time (35 days) reported more cue-driven craving compared to those who only abstained for 7 or 14 days.

That looks a lot like the incubation effect seen in rats, and according to de Wit, may actually be an even more impressive effect than what was seen in animal studies. Whereas rats can be kept totally isolated from drug cues for as long as necessary, the subjects in Bedi’s study were presumably exposed to some smoking-related cues - friends smoking, cigarettes in movies, etc. - during a typical day of their paid abstinence. Yet in the laboratory, the cues still held the power to spark craving, and this craving increased with the number of days of abstinence. In a further surprise, most subjects returned to their smoking habits after their part in the research was finished, regardless of how long they had abstained from smoking for the study.

“I think one of the really interesting things is that almost everybody goes back to smoking, even after a month of not smoking,” de Wit said. “You would think if they could go drug-free for a month it would be pretty easy to stay quit after that, and yet they went back.”

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Alternative medicine tends to live in a battlefield where treatments passed down for centuries clash with the often cold, hard truths of the scientific laboratory. Depending on your bias, one can trust the adherents of ancient practices such as chiropractic medicine or acupuncture, or one can remain skeptical until scientists prove that those therapies represent more than an elaborate placebo effect formalized through numerous generations. Those two worlds usually seem content to co-exist without crossing paths, so it’s interesting when a paper appears in a major journal not only addressing alternative medicine, but actually proposing a biological mechanism for it.

That happened over the weekend in Nature Neuroscience, where a team of researchers mostly from the University of Rochester Medical Center proposed a mechanism for pain relief via acupuncture. The study was centered around acupuncture performed in mice - sadly, there is no video provided - and co-treatment with various drugs to pinpoint (no pun intended) the effects of placing needles at a particular pressure point to relieve a mouse’s paw pain. Researchers concluded that adenosine, a molecule released after cell damage that has previously been identified in sleep regulation and inflammation, accounted for the analgesic effects of acupuncture. That is, when a needle is placed in the body and rotated or heated, adenosine levels are increased in the body and nerves that transmit pain information are inhibited. 

“Acupuncture has been a mainstay of medical treatment in certain parts of the world for 4,000 years, but because it has not been understood completely, many people have remained skeptical,” author Maiken Nedergaard said in a press release. “In this work, we provide information about one physical mechanism through which acupuncture reduces pain in the body.”

Time to book an appointment at the acupuncturist, right? Slow down, the blogosphere responds. Ed Yong at the blog Not Exactly Rocket Science raises a number of thoughtful doubts about the study, from the lack of a control group to a potentially troublesome conflict of interest. Most interesting are Yong’s points about what isn’t in the paper - references to several papers that found little clinical value from acupuncture or studies that found “sham needles” which don’t break the skin are just as effective as the real thing. As such, Yong concludes that the new Nature Neuroscience study offers little support for the value of classic acupuncture, despite its interesting observations about adenosine and pain.

That’s my takeaway as well - acupuncture may be an interesting and time-honored way of inducing the natural pain relief of adenosine, but that doesn’t mean that acupuncture is the only or best way to trigger this response. In fact, some of the data in Nature Neuroscience suggests that drugs which activate the adenosine receptor directly (getting around the whole needle thing) can be effective in reducing neuropathic pain and the pain response to heat. Perhaps the adenosine system offers a new pathway by which people can be distracted from their pain, not unlike the research of Hayley Foo and Peggy Mason on food’s ability to reduce pain. If so, just as the thousand-year-old practice of chewing and smoking poppy plants has given way to fine-tuned opiate pain medications, the scientific mechanism behind acupuncture may be the discovery that renders it obsolete, not legitimate.

Just a few things from around the world of science this week…

Addiction researchers often speculate that abused drugs such as cocaine and nicotine hijack the brain systems responsible for the more natural pursuits of food and sex. Many studies have shown that food, particularly delicious food, can activate brain reward areas, but a new paper by Paul Johnson and Paul Kenny at Scripps Research Institute in Florida made one of the most convincing arguments yet for “food addiction” resembling drug addiction. Rats given unlimited access to a “cafeteria diet” (bacon, cheesecake, frosting and more - yum!) showed not only the expected weight gain, but also a reduced sensitivity to reward. In other words, when rats got fat, the usual good stuff wasn’t quite as rewarding, requiring them to seek even more reward to reach satisfaction.

This reduced sensitivity correlated with a reduction in one type of receptor (D2) for the neurotransmitter dopamine, a reduction seen in drug-addicted animals and people. When researchers used a virus to artificially reduce those receptors, only animals that had previously been exposed to the cafeteria diet showed overeating behavior and reduced reward, suggesting an environmental role also contributes to “food addiction.” It also makes a convincing argument to stay out of the cafeteria.

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A very cool study, but another paper published this week, by scientists from England, Australia and The Netherlands in PLoS Biology, shone a harsh spotlight on the elephant in the room of animal research. Scientific publications are almost always about laboratory or clinical successes, trials or experiments that produced an effect - even if it isn’t always the effect that was expected at the outset. But wherefore the negative results, those experiments where after the dust has settled from statistical analysis, nothing really happened? Only rarely are such non-effects published, a practice that led Emily Sena and colleagues to hypothesize a “publication bias” in animal studies looking at stroke interventions.

Reviewing 16 review studies (papers that aggregate dozens to hundreds of individual research findings), the authors found that only 1 out of 50 papers in those review studies reported negative results. Anyone who has worked in a lab knows that far fewer than 98 percent of all experiments show an effect, leading the authors to believe that many negative results go unreported. That’s kind of a big deal. For one, animal studies that didn’t work may be needlessly replicated by scientists who didn’t realize they’d already been tried out, wasting time, money, and laboratory animals’ lives. For two, when that research is translated from animals to humans, researchers may overestimate the efficacy of those interventions - a potential explanation for why the jump from lab rat to patient is so often unsuccessful. Obviously, if this is a problem for stroke interventions, one can imagine it affecting biomedical research of all stripes. But until more journals are willing to publish negative results and scientists willing to check their ego and publish those experimental duds, it’s an issue that’s not going away.

A lengthier analysis of this paper and similar efforts to self-police science is recommended reading at Respectful Insolence.

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Much has been written this week about the potentially landmark legal decision to revoke the patents held by a private company on BRCA-1 and BRCA-2, genes that signal a predisposition to breast or uterine cancer. I got the most information on the case from Genomics Law Report, a blog run by lawyer Daniel Vorhaus - particularly this post on the legal nitty-gritty and what happens next. Deborah Shelton of the Chicago Tribune (my former newsroom cubicle neighbor) also had a more accessible write-up in today’s paper.

Who says scientists don’t have a sense of humor? Check out this roundup by Nature News of the best science-related April Fool’s gags, including the new journal pictured above (I chuckled at “Evolution: Why Won’t It Stop?”).

University of Chicago internal medicine resident Shantanu Nundy is currently in rural Uganda working at a clinic for pregnant mothers, and he’s blogging about it here. Nundy, who apparently does not sleep, also wrote a book called Stay Healthy at Every Age: What Your Doctor Wants You to Know that is due to be released soon.

Finally, don’t get your medical information from twitter. Save it for Justin Bieber news.

From Rose et al., PNAS, 2010

For the return of Linkage after a week’s dormancy, here’s an interesting paper from the journal Proceedings of the Natural Academy of Sciences - PNAS, in scientific shorthand - a quickfire roundup.

Radioactive Cigarettes

As one of the most popular addictive substances in the world, tobacco has drawn a lot of research attention. Scientists have long sought the mechanisms by which tobacco - whether smoked, chewed or snuffed - affects the brain, creating its powerful dependence in users and the massive profits and public health problems therein. That happens to be the sub-field in which I did my graduate research, but that’s only part of why a paper this week from scientists at Duke and Wake Forest caught my eye. Measuring nicotine concentrations in the brain while a human subject smokes a cigarette? Pretty cool. Doing it with radioactive cigarettes? Extra cool.

Don’t worry - this process isn’t going to turn anybody into some kind of chain-smoking Hulk. The method was a variation on positron emission tomography, more commonly known as PET scans, used regularly by hospitals to obtain high-quality real-time medical images. In a typical PET scan, the patient drinks or is injected with a radioactive tracer, a safe isotope that allows the scanning machine to map internal organs so doctors can find tumors, measure drug metabolism, or observe brain activity.

In this study, researchers gave test subjects cigarettes loaded with radioactive nicotine - a normal carbon on the nicotine was replaced with a radioactive carbon isotope. The substitution allowed them to track the movement of nicotine in real time as a subject smoked, following it along its path from mouth to lungs to brain. When they did this, two surprises were found: 1) Nicotine concentrations in the brain rise gradually over the course of a cigarette, not in spikes corresponding to each “puff,” and 2) Under controlled circumstances, regular smokers actually achieve lower brain nicotine concentrations than casual smokers.

That latter finding has to do, strangely, with the absorption of nicotine from the lungs to blood, which was found to be slower in heavy smokers. But not to be thwarted, the smokers compensate by taking deeper puffs of their cigarettes, the researchers found, offsetting the slower absorption. The main application of that knowledge is to other studies of nicotine in the brain that are trying to simulate the natural concentrations experienced after a cigarette - like my old experiments which tested the effects of nicotine on a slice of rat brain kept alive for several hours in a dish. But for everyone else, at least now you know what a brain on cigarettes looks like, without the use of egg metaphors.

Elsewhere…

I want to link to almost every post Jonah Lehrer makes on his blog (and often do through my twitter account), but this one on creativity, brain hemisphere damage and the effects of marijuana is even a cut above his usual musings. Bonus insight from Vaughan Bell at Mind Hacks, making this a big old jam session of my favorite science bloggers.

Emil Coccaro, chair of psychiatry at the University of Chicago Medical Center, appeared in a Wall Street Journal article about when having a foul temper becomes a psychiatric condition called intermittent explosive disorder. Watch out for an article on Coccaro’s IED research appearing here soon.

We’ve talked a lot here about using DNA sequences as a clinical tool for cancer treatment. This New York Times article suggests that the answers may reside in mitochondrial, rather than nuclear, DNA.

Our own Jerry Coyne blogs about the viral science photo of the week, the all-black king penguin. And talks to the Associated Press about the poor quality of two popular biology textbooks for home-schooled kids.

Speaking of Coyne, science and religion are increasingly antagonistic bedfellows, but this article by Dave Munger in Seed gives a good overview of one scientific DMZ where they can reasonably intersect: the study of why religious beliefs evolved in humans.

Please welcome Laurel Mylonas-Orwig, author of today’s post and a new contributor to the blog!

Every two years, the best athletes in the world gather to compete in the modern Olympic Games. Against a backdrop of sand or snow, these seemingly superhuman competitors push their bodies to perform feats that would be impossible for the average person. Yet in the past few decades, concerns have mounted over whether some participants have gone beyond what the human body is truly capable of, relying on performance enhancers to reach new heights. In the 2004 Summer Olympics, a record number of athletes tested positive for banned substances, leading to several disqualifications and stripped medals. But in the just-completed 2010 Winter Olympics in Vancouver, drug testing has only caught two athletes thus far.

Despite this low number, experts are skeptical that athletes have stopped looking for illegal ways to gain a competitive edge. Instead, officials suspect that those who want to cheat have found ways around the current doping tests. The biggest elephant currently in the drug-testing room is an enhancement that is not yet reliably detectable, or even proven to be scientifically possible: gene doping.

Gene doping is a new and dangerous frontier in performance enhancement. An offshoot of gene therapy, gene doping may someday allow athletes to produce extra copies of genes that provide a competitive advantage such as increased muscle mass or endurance. At present, however, both gene doping and gene therapy remain largely untested in humans. Although some animal studies have shown promising results, others have demonstrated deadly side effects, leaving the effects of such treatments questionable at best.

Natural Enhancement?

When research into gene therapy began, it was not intended to yield performance-enhancing technology. Gene therapy is designed to treat debilitating or deadly medical conditions via the insertion of corrective genes into the body’s cells. But the theory behind gene therapy indicates that if the right gene were to be spliced into a healthy person’s DNA, a competitive edge could be gained. One example is that of erythropoietin, more commonly known as “Epo.” First purified in the late 1960’s by University of Chicago researcher Eugene Goldwasser, Epo is a hormone that promotes the production of oxygen-carrying red blood cells.

In 1997, a group of University of Chicago scientists led by Dr. Jeffrey Leiden experimented with Epo gene therapy as a treatment for Epo-responsive anemia, a debilitating condition caused by chronic renal failure. The study focused on the safety and efficacy of injecting a virus carrying the gene into the muscles of mice and non-human primates. Overall, the experiments proved successful: researchers were able to establish a threshold dose required for long-term Epo expression, and the elevated hematocrit, or red blood cell volume, in the animals that underwent the treatment led to increased aerobic ability. More importantly, no adverse reactions to the treatment were observed.

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