Imagine if your comfortable existence was suddenly and traumatically disrupted by a disaster. Your home is destroyed, food becomes scarce, and social structures suddenly break down. Even the most civilized people would respond to this situation with desperation, doing whatever it takes to survive in the short-term without the usual considerations for the long term.

Now imagine you are a bacterium, living inside the human gut (this might take a bit more imagination). For as long as you can remember, everything has been cool there - a steady stream of nutrients pass by to feed on, the police force of the body’s immune system does not perceive you as a threat, and a happy society has been established with the thousands of other bacterial species in the area. But suddenly, the world as you know it is shaken. The human in which you have made your home contracts a serious illness, and undergoes surgery and intense antibiotic treatment. Millions of your fellow citizens are killed, the food supply dries up, the immune system declares martial law. Facing this desperate situation, bacteria tend to act just like humans would - they riot.

This pattern of ecological collapse leading to chaos may underlie one of the most difficult problems facing health care today: hospital infections. Since surgeon Joseph Lister discovered in the 1860’s that carbolic acid can be used to sterilize surgical instruments and wounds to reduce infection rates, hospitals have grown obsessed with cleanliness to protect patients from bacterial invasion. Yet even perfect diligence cannot prevent serious infections from occurring in a small population of patients, causing scientists such as John Alverdy, professor of surgery at the Medical Center, to ask: Could the threat of bacterial infection be coming from within?

“It’s a new way of thinking about infection, because we’re already doing already we can - washing our hands, sterilizing the site, giving our patients antibiotics - and yet some of the infections seem to be getting worse,” Alverdy said. “There has to be a strategy change, and I think we’re at the forefront of understanding that.”

Alverdy’s group has spent the last decade studying a member of the gut microbiome (the world of bacteria living inside our digestive system), called Pseudomonas aeruginosa. Most of the time, Pseudomonas is a passive colonizer of the human body, an “accidental pathogen” that we pick up through our diets or other environmental exposure that causes no harm. But when the body is severely stressed by a surgical procedure, illness, chemotherapy, or radiation, Pseudomonas occasionally panics and becomes an extremely dangerous inhabitant. Alerted to the body’s emergency by immune system factors and starved for food, it begins tunneling through the lining of the gut to invade the unfortunate patient’s blood. Once the bacteria goes on the attack, it’s very difficult to treat, giving it the highest mortality rate of any hospital infection.

“I have seen some people postulate that Pseudomonas isn’t a very virulent pathogen, and I say ‘what are you talking about?’,” Alverdy said. “If you provoke it the right way, it will kill everything in its wake. It’s very virulent.”

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Photo by Bruce Powell

Yesterday wasn’t just St. Patrick’s Day for fourth-year medical students around the country - it was also Match Day, the tense and celebratory day when aspiring doctors learn the residency program where they will spend their next 3-7 years. At the Pritzker School of Medicine, green-clad students and supporters absolutely packed the hospital’s Billings Auditorium for the big event Thursday morning, cheering their peers as they were called one by one at random to collect their match envelope. In a local tradition, it literally pays to go last, as students throw into an informal prize pot for whoever has to wait and squirm the longest to pick up their envelope (second-to-last gets a Hershey bar as consolation). In the video below, you can see some of that process - including the outcry when the last envelopes are miscounted - followed by the amazing tension-release of the countdown and unison envelope opening.

The numbers from the day are just as exciting as the video. At Pritzker (recently ranked #12 among medical schools by US News and World Report), 110 students were matched in 24 specialties at 46 institutions, including 23 students who will stay with us here at the Medical Center. The most popular specialties for Pritzker students were internal medicine (25% of the class), general surgery (11%), and pediatrics (11%). Nationally, trends continued to shift for the second consecutive year toward primary care specialties such as internal medicine, family medicine, and pediatrics, according to the National Residency Matching Program, a step in the right direction to meet some of the increased demand for primary care doctors expected in the wake of health care reform. MedPageToday’s Kristina Fiore breaks down the numbers.

Podcast 0.3: Transplants, Rock-Paper-Scissors Ecology, and More

We have settled on a name for our young research podcast: Bench to Bedside. However, we are still keeping the training wheels on as we work out the technical kinks and explore the best ways to deliver audio versions of our latest research and medical stories. Please enjoy the third installment of our podcast, featuring a recent coast-to-coast kidney transplant chain that involved the Medical Center, how Rock-Paper-Scissors can explain biodiversity, the fight against indoor air pollution in Nigeria, and the new numbers on the eating disorders epidemic in the United States. As always, we would love to hear feedback on what we’re doing right and wrong at robert.mitchum@uchospitals.edu or dianna.douglas@uchospitals.edu.

Bench to Bedside Episode #0.3 by robmitchum

Elsewhere…

Some people keep ant farms, some people keep multiple flasks of bacteria growing for 13 years (and counting) to study evolution. Ed Yong writes about experiments from Michigan State University that show “tortoise” bacteria can beat out “hare” bacteria over the long run. (And if you’re a science communicator of any sort, do listen to Ed and Carl Zimmer’s “Death to Obfuscation” session from January’s Science Online meeting)

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Electronic health records are a hot topic in the world of medicine, as hospitals implement new computerized systems to meet federal incentives. Proponents of replacing paper records with electronic health records (EHR) in hospitals and other health care settings argue that the update will improve the efficiency of health care, cutting costs and making life easier for patients and doctors. But a less popularized - and probably more immediate - effect of the EHR wave will be felt by clinical researchers, who will suddenly have a flood of medical data where there once was a drought.

This new EHR-enabled world of clinical research was featured in a recent lecture at the Department of Medicine Grand Rounds by Ari Robicsek, visiting from the Medical Center’s partner institution in Evanston, NorthShore University Health System. Robicsek is an infectious disease specialist and a self-described “accidental informaticist,” a physician and researcher who found himself drawn to EHRs as a tool to address important clinical questions. As an early adopter of paperless medical records, NorthShore has had 8 years to build a “data warehouse” that can be used for research projects. While the Medical Center works toward the next phase of its own EHR launch, called Phoenix, Robicsek’s examples were an exciting peek at how the new resource can be used to prevent hospital-acquired infections and make the most significant change to the definition of fever in 140 years.

“These are, I hope, a series of interesting illustrations of the increasingly amazing things that researchers and hospital systems are capable of doing because of the growing informatics resources available to us,” Robicsek said.

A top priority and concern for any hospital is reducing the spread of bacterial such as MRSA, which can infect sick patients with suppressed immune systems during their inpatient stay. In the last decade, hospitals have launched intensive screening programs to find patients who are carrying these bacterial strains as soon as they are admitted to the hospital, so that extra precautions can be taken. However, it’s not cheap to test every single patient, and false positives in the tests create unnecessary expense. Being able to target tests to patients more likely to be colonized by MRSA could save millions of dollars - a shift that Congress has ordered, without offering any help on just how to find those “magical” high-risk patients, Robicsek said.

Sounds like a job for the electronic health record! Because NorthShore has been adding the results of its MRSA screening tests to patients’ electronic records, Robicsek and colleagues were able to quickly comb through the data of more than 23,000 patients to find characteristics that predicted a high chance of carrying the bacteria. Instead of pulling each paper record by hand as in the old days, computer models could be built to find predictors of risk. When tested in a second batch of data (built from more than 26,000 patients), the models published earlier this year could identify the 30 percent of “high-risk” patients who account for the majority of positive MRSA tests. If implemented (as NorthShore plans to do later this year), such models could direct testing to those patients most likely to be an infection risk, rather than testing willy-nilly and racking up giant expenses.

Besides alerting physicians to clinical threats, electronic health records can also help them do more with data they’ve been collecting the old-fashioned way for centuries. Fever might be the most basic biometric, simple enough for Moms to test informally at home with the back of their hand. But the meaning of fever has changed little since Carl Reinhold August Wunderlich established the normal body temperature of humans (roughly 37° Celsius or 98.6° Fahrenheit) in 1871, Robicsek said.

“[Wunderlich] is thought over the course of his career to have taken the temperature of some 25,000 individuals, and it was his monograph on clinical thermometry that caused temperature vigilance to be introduced into routine clinical care,” Robicsek said. “Remarkably, there has been very little subsequent work validating his data…almost nobody has looked at this in the setting of physiological perturbation,” - in other words, asking what is a “normal” fever after a surgery, and when is it a cause for worry.

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The immune system is designed to protect the body against foreign invaders, neutralizing disease and infection. But organisms are all too happy to invite invasions several times a day through a seemingly innocuous act: eating. When food enters the digestive system, it has to be dealt with by the immune system just like everything else that finds its way into the body. Under normal circumstances, the immune defenses recognize that food is not a threat and lay down their arms. But in the case of food allergies or digestive disorders, certain types of food are treated as dangerous enemies, with unpleasant consequences for the person.

Celiac disease is one such disorder, where patients suffer painful symptoms after consuming gluten, a dietary protein found in wheat, barley, and rye. Rather than building up a tolerance to the protein that allows for untroubled digestion, the immune system treats gluten as a threat and activates its defensive weapons, including inflammatory factors that attack the lining of the small intestine. As a result, an innocent piece of bread for most people can be absolute misery for one of the 3 million Americans with celiac disease, causing abdominal pain, diarrhea, vomiting, and more serious chronic symptoms.

So far, the best treatment for celiac disease is plain old avoidance - a gluten-free diet to prevent digestive symptoms. Because the immune system is so complex, researchers have struggled to find the exact components responsible for the intolerance to gluten. But clues abound from patients treated at clinics such as the University of Chicago Celiac Disease Center, including unusually high levels of an immune factor called interleukin-15 in the patients’ intestines. That clue was the starting point for a new study published last week in Nature and led by Bana Jabri, associate professor of medicine at the Medical Center, that tracks down two triggers of celiac disease that may prove crucial to better treatments.

Interleukins are the messengers of the immune system, carrying signals that instruct the body’s defensive force to ramp up or stand down, depending on their context. In the gut, interleukin-15, or IL-15, was found by Jabri and colleagues to inhibit the activity of regulatory T cells, peacekeepers that block the immune response on targets that are considered non-threatening. After repeated exposure to gluten, most people build up a tolerance to the protein and are able to digest the nutrients in grains and breads without trouble. But for people with celiac disease, elevated IL-15 may interfere with this cease fire.

The researchers further tested their theory by engineering mice that over-expressed IL-15 in their digestive systems. When these mice were fed a protein found in eggs, another common food allergy trigger, the result was inflammation instead of tolerance - as is seen in celiac disease with gluten. Conversely, blocking IL-15 activity restored the normal response in the mice.

“We found that having elevated levels of IL-15 in the gut could initiate all the early stages of celiac disease in those who were genetically susceptible, and that blocking IL-15 could prevent the disease in our mouse model,” Jabri told John Easton.

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Two years ago, fear about the the novel H1N1 flu strain spread far more quickly than the virus itself, fueled by equal parts scientific concern about its resemblance to the deadly 1918 flu and media hysteria. In those early days, with a vaccine still months away, scientists were working quickly to develop protections and treatments for the flu for those at high risk of infection and serious illness. As a Chicago Tribune reporter covering the impending pandemic, one of the flu experts I spoke to about these efforts was Patrick Wilson, assistant professor of medicine at the University of Chicago. Wilson, in collaboration with scientists from the CDC and Emory University, was looking at the antibodies produced by the first people exposed to H1N1, to see if they could be used as emergency “vaccines” for health care workers that would be exposed to infected patients.

Though the worldwide pandemic did not measure up to initial concerns, it remained a dangerous and virulent flu, infecting 60 million and hospitalizing more than 250,000 in the United States alone. And while it was not urgently needed, Wilson’s research on the antibodies for H1N1 continued, in order to learn about how the body defended itself against this viral invader. As published this week in the Journal of Experimental Medicine, that project led to a surprising conclusion: the antibodies produced to fight the 2009 H1N1 virus were not only successful in warding off that virus, but might be protective against many different types of influenza - including the historically nasty 1918 strain.

“The result is something like the Holy Grail for flu-vaccine research,” Wilson said. “It demonstrates how to make a single vaccine that could potentially provide immunity to all influenza. The surprise was that such a very different influenza strain, as opposed to the most common strains, could lead us to something so widely applicable.”

When the body reacts to an influenza virus, or any other infectious disease, it creates antibodies that target a specific segment of the invading virus or bacteria to kill or neutralize it. But because influenza viruses are constantly mutating into new forms, antibodies your immune system generated for previous seasons’ strains may not be protective against new strains. Hence, the need for a yearly flu shot, which contains inactivated forms of the viruses that scientists predict will become common in the next season. The vaccine spurs the production of antibodies against those strains, offering protection against infection.

For Wilson and his collaborators, the original idea was to take antibodies from patients exposed to H1N1 in its earliest days and use them to either protect others from infection or treat those who had already been infected. Initial experiments on the antibodies’ power of recognition proved successful - as predicted, many of the antibodies harvested from the white blood cells of H1N1 patients were able to bind the flu strain in an assay. But then, a surprise: when tested with seasonal flu strains from previous years, the antibodies could bind those viruses as well. Researchers threw the last 10 years of seasonal flu, the deadly 1918 virus, and even a dangerous but rare H5N1 avian flu at the antibodies and found they could neutralize them all.

Attacking a virus in a dish is one thing, but the big test would be whether these antibodies could fight infections in the body. Mice were given the antibodies before receiving a dose of the 2009 H1N1 strain, and were found to be protected against the virus as if given a vaccine. When mice were dosed with H1N1 first, then given antibodies as much as 3 days later, the antibodies successfully fought off the infection; by day 12, the antibody-treated mice were free of virus, while the unfortunate control mice all perished by day 7 or 8. The antibodies went on to reign victorious over influenza in further experiments with seasonal flu, the 1918 flu, and avian flu.

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The immune system relies heavily on memory and recognition, with its success dependent on marshaling defenses against only the right infectious invaders. Scientists are finding that this memory requires a lot of moving parts, including molecules that grab pieces of bacteria and viruses, specialized cells that can determine whether those pieces are dangerous or not, and cells that attack and kill those microbes if they are ruled to be a threat. The key at each step of this complex system is specificity; if each component only binds or attacks certain types of molecules, it makes the process of remembering the correct response that much easier. As with a condo building, having the right locksmith can make all the difference.

Bacteria are largely made up of proteins and lipids, and when they first get inside a cell, the initial defense system strips them down to these parts. For proteins broken up into smaller pieces called peptides, the MHC molecules are the designated grabbers, binding the molecules and bringing them to the cell surface for recognition. But for lipids, a different group of molecules, the CD1 family, performs this task. Because lipids make up the bacterial cell wall - the critical outer barrier of the microbe - they are good, reliable candidates for jogging the immune system’s memory and initiating a response.

“It’s a really excellent way of recognizing a bacterial lipid, because they look a lot different than what they look like in us,” said Erin Adams, assistant professor of biochemistry & molecular biophysics at the University of Chicago. “If you are a bacteria, you can mutate your protein to evade the immune response and not be recognized any more, but it’s really difficult to change the structure of a lipid. If you screw it up too much, then the bacteria doesn’t survive.”

Understanding more about how these CD1 molecules function could be helpful in building better vaccines or treatments against bacteria and viruses. But the traditional scientific approach of taking a snapshot of these molecules (through the method of X-ray crystallography) was frustratingly difficult. So a multi-disciplinary team led by Louise Scharf in Adams’ laboratory set about using some molecular engineering to solve that problem, and their work was published last month in the journal Immunity.

The mission was to catch one of the CD1 family, CD1c, in the act of binding with a bacterial lipid; in this case, a component of the bacteria that causes tuberculosis called mannosyl-ß1-phosphomycoketide (MPM, for much-needed short). The protein was normally too unstable for crystallography, so Scharf and colleagues meticulously changed pieces of CD1c to create a more stable structure, without betraying the molecule’s original function.

“We did a lot of tests to make sure that the protein that we made, our Frankenstein protein, was only Frankenstein in the bits that didn’t count, the structural parts of the protein,” Adams said. “We had to keep validating along the way, step by step, to make sure we weren’t creating a monster.”

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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.

Photo by Aaron Logan (Wikimedia Commons)

Within the primate family, relatives are not treated equally by disease. While AIDS, malaria, and cancer kill millions of humans each year around the world, non-human primates largely shrug these diseases off. For example, chimpanzees can be infected with a form of HIV (called Simian Immunodeficiency Virus, or SIV, in their case), but the disease rarely progresses to AIDS. What is different about the immune system of humans and their primate peers to create this startling difference in disease susceptibility?

The obvious answer, as always, is evolution. When humans and chimpanzees went their separate genetic ways from their common ancestor and started living in different environments with different diseases, their immune systems also diverged. Fortunately, the story of that divergence can still be read in the genes, provided you have the right equipment to do so. Luis Barreiro, a postdoctoral researcher in the human genetics laboratory of Yoav Gilad, has started looking for that story by comparing the immune pathways of different primate species.

The first such comparison, published last week in PLoS Genetics, focused on the innate immune system of humans, chimpanzees, and rhesus monkeys. Unlike the better-known adaptive immune system, which produces antibodies to fight specific viruses and bacteria, the innate immune system is a less specific system, the first line of defense against infection. Pattern recognition receptors, such as the toll-like receptor (TLR) family, recognize common features of pathogens and activate genes to begin the fightback.

“Each time you have a pathogen that invades your body, you have this first alert, the first genes that are going to fight the infection,” Barreiro said. “It’s probably the most ancient mechanism of immune defense; it’s present in all species, whereas adaptive immune response is much more recent.”

Barreiro, with John Marioni, Ran Blekhman, and Matthew Stephens, isolated blood cells from the three species and stimulated them with lipopolysaccharide, a molecule found in the membrane of gram-negative bacteria that stimulates TLRs. The researchers then measured gene expression - genes activated or deactivated by the stimulus - across the three species, looking for differences in immune system responses.

The experiment showed that the “core” general response of the innate immune system was very similar between the three primates, with the majority of affected genes shared across the species - evolution has not changed this process very much. But when researchers dialed in on the specific response to viruses, more species differences in patterns of gene expression appeared, suggesting rapid evolution of the immune defenses to these pathogens.

“That is interesting, because we know that viruses are evolving very, very quickly,” Barreiro said. “So we can imagine that the immune response to fight these viruses also has to evolve quickly to adapt to these changes.” [an example of the Red Queen Hypothesis]

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If a parasite infected the brains of 2 to 3 billion people, up to one-half of the world’s population, one would probably consider it a pretty serious public health emergency. But such a situation already exists, with the parasite Toxoplasma gondii, the cause of the disease toxoplasmosis. The parasite is the most common infectious cause of retinal damage, and can cause brain damage or death in its most severe forms.

Most people hear of toxoplasmosis from cases of mother-fetus transmission, the reason why pregnant women are advised to stay away from cats, who are known carriers and dispersers of the parasite. Toxoplasmosis can also flare up in people with compromised immune systems, due to diseases like HIV, cancer, and autoimmune disorders. But the Toxoplasma gondii parasite is also an apparently quiet, untreatable houseguest in the brains of billions more people, where its possible role in seizure disorders, schizophrenia, and memory loss is just starting to be investigated.

With a widespread infection where the proven effects are already scary and the unproven effects may be even worse, it would be great to have vaccine protection against toxoplasmosis. But while vaccines are typically designed for unwelcome visitors of bacterial or viral form, they are not normally used to prevent infection from protozoan parasites like Toxoplasma gondii. That did not discourage the laboratory of Rima McLeod, who has recently published three papers with collaborators on two separate potential vaccination strategies against toxoplasmosis.

The most direct vaccine strategy - used against polio and chicken pox, for example - is to take a live pathogen and render it harmless. When introduced into a subject as part of a vaccine, the defanged invader inspires the immune system to respond as it would the real thing, increasing its defenses for when the actual virus attacks.

In a paper published at PLoS ONE, a group led by Samuel Hutson created a strong candidate for this type of vaccine by creating a mutant Toxoplasma gondii. Constructs created by collaborators in the Netherlands modified the promoter of a ribosomal protein in the parasite so that scientists could place it in a state where it became unable to proliferate. When injected into mice, this “trapped” strain disappears within 10 days, but not before educating the immune system on how to fight off subsequent infection by the real parasite.

“It is extraordinarily, robustly protective,” McLeod said. “It was 100 percent protective for mice against large numbers of the homologous parasite strains, and it was also very good at protecting against heterologous parasites as well. It made a very effective live vaccine.”

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The past few decades have brought astounding progress in fighting the scourge of infectious disease in developing countries. It’s remarkable to think that a disease such as smallpox, which killed 50 million people a year only 50 years ago, has been successfully eradicated from the world. Similarly, polio has been stamped down to only rare outbreaks, and great strides have been made against HIV/AIDS and tuberculosis in poor countries.

But the fight against infectious disease is only half the battle in global health. In fact, it’s less than half, said Abdallah Daar of the University of Toronto in his Nov. 3 talk for the MacLean Center for Clinical Medical Ethics Seminar Series. More people in the developing world die from chronic, non-communicable diseases like diabetes and cancer than from infectious disease, nutritional deficiencies, or inherited conditions combined. While chronic diseases dominate health care in the United States and Europe, efforts to fight those disease in poorer countries have lagged far behind the funding for infectious disease.

“About 60 million people die each year, and people imagine that a lot of people in the developing world die from infectious diseases. Well, it’s not so,” said Daar, the Senior Scientist and Director of Ethics and Commercialization at the University of Toronto’s McLaughlin-Rotman Centre for Global Health. “Chronic disease…is an area that has been totally neglected in the developing world.”

To fill in this considerable gap, Daar’s group has helped coordinate new initiatives with the Canadian government and research agencies around the world. The Global Alliance for Chronic Disease, which brings together six scientific funding bodies from the US, Canada, China, India, England, and Australia, was created to address the priorities laid out by Daar and colleagues in a 2007 editorial. “Inaction is costing millions of premature deaths throughout the world,” they wrote.

The effort plans to go after worldwide chronic disease on several fronts, from modifying risk factors such as diet, exercise and smoking to advocating for healthier government policy and health systems to working with businesses to deliver cheaper, more effective care to underserved populations.

“We know how to treat hypertension in one person. We know how to treat hypertension in a classroom. But how do you treat hypertension in a whole country? We don’t know how to do that,” Daar said. “We need to learn how to take evidence and how to scale it up and interact with policymakers and get them to buy in. So if you do a screening program, and it’s very successful and you save many lives, how do you get the policymakers to say yes, we’ll do this on a national scale and save even more lives?”

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When the novel H1N1 flu virus began to appear in North America and Europe in Spring 2009, it contained some worryingly familiar signs to flu experts. The new strain appeared suddenly in a season when flu typically declines, spread at a rapid pace, and seemed to disproportionately affect the young more than the old. The last influenza to display those features was the notorious 1918 flu, which killed as many as 100 million people around the world before burning out a year later.

“It was the most devastating infectious diseases episode in world history,” said Michael David, Instructor of Medicine at the University of Chicago Medical Center. “In numbers, it was probably 10 to 100 times more severe in terms of the absolute number of people killed than were killed in The Black Death.”

Of course, last year’s H1N1 pandemic was nowhere near as deadly, causing only an estimated 12,500 deaths in the United States despite approximately 60 million infections. The low mortality among elderly populations from H1N1 may have actually made the 2009-10 flu season less deadly than usual, as the Centers for Disease Control and Prevention estimate a yearly average of roughly 36,000 influenza deaths. But comparing 1918 to 2009 still reveals interesting similarities, David said in his October 14 talk at the Department of Pediatric Grand Rounds.

In the spring, when the virus first showed up on public health radar as a novel strain with all the right ingredients for a pandemic (jumped from animal to human, easily transmissable), the worst case scenario of 1918 couldn’t be ruled out. Like the 2009 strain, the 1918 influenza also made a relatively modest appearance in the spring, David said - graphs of the pandemic’s death rate revealed a small spike in the summer. Come October, that mild hill was overwhelmed by the shocking spike of influenza deaths that raged across the United States and Europe. In 8 weeks, 25 million people were infected with the virus, and some 600,000 died - in the U.S. alone.

“That’s more than the number of soldiers that were killed on both sides in the U.S. Civil War,” David said. “It’s something that’s really hard for us to grasp with our imaginations.”

[If you have a JAMA subscription, you can read this 1918 first-hand account of the pandemic at Cook County Hospital in Chicago - "During the past five weeks, more than 2,000 patients were admitted to the hospital. The disease is highly contagious and the mortality among our patients has totaled 31 percent. The epidemic has seriously crippled the medical and most especially the nursing staff of our hospital."]

In addition to its ferocious spread and mortality rate, the 1918 influenza was also unusual for the victims it chose: 20 percent of the deaths were in children under the age of 5, and 15 percent were between 20 and 25 years old. The line formed by these two mortality peaks combined with deaths in the elderly formed the pandemic’s characteristic “W curve” (pictured above), in contrast to the usual “U curve” seen when only the very young and old die from influenza.

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RN Debbie Pienta of the Student Care Center at the University of Chicago gives a flu shot. (Photo by Yvette Marie Dostatni)

Until last year, the advent of the new influenza season was a pretty routine event on the health care calendar. Around October, people would be urged to receive vaccinations against the viral strains expected to plague North America in the coming months, with young children and older adults encouraged more strongly to get their annual shot. Other folks received their vaccine with all the enthusiasm of a trip to the dentist - something you know is good for you, but not exactly an urgent concern.

That all changed last year, thanks to the novel H1N1 virus, aka swine flu, aka the global flu pandemic. Suddenly, seasonal flu clinics used to a slow trickle of customers were faced with lines out the door and around the block, as the combination of limited H1N1 vaccine supply and media hysteria created unusual demand. Caught short by the late-breaking new strain, suppliers had to prepare a separate vaccine for the H1N1 virus, requiring people to get stuck with a needle twice for full protection.

The good news heading into the 2010-11 flu season is that many of those logistical headaches have been resolved. With no new strains rearing their head since last year, vaccine makers were able to consolidate protection against H1N1 and two seasonal strains into one injection or nasal spray. The Centers for Disease Control and Prevention recommendations have also been simplified: all people above the age of 6 months are advised to get the flu vaccine, full stop. All signs this season also point to better preparedness across the board from government and private organizations dispensing the vaccines - local Walgreens in Chicago were advertising vaccine availability well in mid-September.

To raise awareness of vaccine availability on the University of Chicago campus, ScienceLife talked to two of our flu experts: Stephen Weber, medical director of infection control at the Medical Center, and Ken Alexander, chief of pediatric infectious diseases. Here’s a few of their answers about this coming flu season and the research taking place one year post-epidemic.

Q: If 2010-11 is expected to be a routine flu season, what does that mean?

Weber: A regular flu season doesn’t mean that it’s easy or that people don’t get sick. We have to remember that while flu is a very common illness, folks who are not vaccinated are at an increased risk.

In many resepects we return to our usual state of flu awareness and preparedness. Bearing in mind, we are talking about infections that kill 24,000 Americans each year, and that’s not something that we want to neglect or that we want to be anything but vigilant about. We have an opportunity to save lives, and whether it happens to be a pandemic or a seasonal year, we still have an important responsibility.

Q: Why is it especially important for parents of infants to be immunized against flu?

Alexander: It’s the notion of a “cocoon.” The idea here is that babies under 6 months don’t respond well to flu vaccine, so we don’t get give shots. So you have this window of vulnerability, and babies are at high risk. With cocoon immunization, if can’t immunize the kid, we can immunize everybody around the child.

There are good data on pertussis transmission to babies, that they receive the virus one-third of the time from the mother, a quarter of the time from dad, and a quarter from their grandparents. Flu is probably pretty much the same, and the idea is we can protect them if we immunize people around the baby.

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Many people take pride in never missing a day of work, and fighting through what they perceive as a minor illness to put in a full shift at the office. But what if your office is a hospital ward? Doctors who show up for work sick run the risk of spreading their illness to patients, further complicating their health issues. But with the tight schedules and long hours of the hospital, there’s even more pressure to get out of bed and fight through your sniffles (or worse).

Medical residents, physicians in their first few years out of medical school, have the tightest schedules and longest hours of all, and a study by University of Chicago and Massachusetts General Hospital researchers found that population to be especially guilty of “presenteeism.” In the wake of last year’s H1N1 flu epidemic, concerns about this bad habit have grown, and Vineet Arora, Anupam Jena and colleagues surveyed residents from 12 medical centers. In a study published in the Journal of the American Medical Association, they found that 60 percent of residents surveyed showed up to work sick at least once in the academic year 2008-09.

“Hospitals need to build systems and create a workplace culture that enables all caregivers, not just residents, to feel comfortable calling in sick,” Arora said of the results. “Their colleagues and their patients will thank them.”

See coverage at CNN, Scientific American, and AP.

Elsewhere…

How many species bear your name? If your name is Robert F. Inger, the answer is more than 50, ranging from Calamalaria ingeri to Ingerna charlesdarwini. That’s the kind of list you rack up when you’ve spent seven decades studying amphibians and reptiles in Borneo, Thailand, Malaysia, India, and China. Last week, Inger - a graduate of the University of Chicago and curator emeritus at the Field Museum in Chicago - celebrated his 90th birthday, and his colleagues put together a website to celebrate the occasion.

The official opening of the University of Chicago Center in Beijing was celebrated this week, a space designed to foster collaboration between our faculty and Chinese researchers and experts. As this feature describes, many such partnerships are already underway, including the AIDS education efforts of professor of medicine Renslow Sherer and fossil-hunting projects by paleontologist Paul Sereno. By a stroke of luck, ScienceLife will write about another Sino-UofC research collaboration next week - stay tuned!

Our contribution to President Obama’s Commission for the Study of Bioethical Issues, physician/bioethicist/friar Daniel Sulmasy, was profiled in the Chicago Tribune.

Another genetic sequencing race, this time between…Mars and Hershey’s? The Snickers maker struck the first blow with Wednesday’s online public domain publication of the Cacao Genome Database, while a group funded by Hershey’s hopes to publish their sequence in a journal soon. The competition is both delicious and beneficial, experts said, and may someday yield more efficient cocoa famring as well as chocolate that is both healthier and better-tasting. Yes, please.

The human body is not just an organism, it’s an ecosystem. To the billions of microscopic bacteria, viruses and fungi living in the various nooks and crannies of our intestines, mouth, nose, and other areas, we are the world, the environment that drives their evolution. Though scientists and physicians have long known that humans are housing projects for a wide array of species, research on the clinical impact that microscopic population exerts upon its host is just starting to establish momentum. Many researchers are now exploring links between what’s become known as the “microbiome” and everything from infectious disease to diabetes and obesity to psychiatric disorders.

An official seal of approval was stamped on to these efforts by the National Institutes of Health in 2008, with the announcement of the $157 million “Human Microbiome Project.” Tuesday, the project was given another $42 million bolus of funding, $1.1 million of which went to a team of University of Chicago and Argonne National Laboratory scientists. But research into the microbiome is already yielding interesting results on the world inside your gut, and how it is affected by diet from the very start of life.

The debate over giving babies breast milk or formula has swung like a pendulum since the mid-20th-century, with medical societies now endorsing breastfeeding infants whenever possible. Studies have shown that breastfeeding has advantages in protecting infants from infection and disease and provides essential, easily-digestible nutrients. But what is the biological basis for breast milk’s superiority? Scientists have speculated that it has to do with the effect of diet on the microbes of the gut. In a paper published last month at PLoS ONE, Michael Morowitz, assistant professor of surgery and pediatrics at Comer Children’s Hospital, sought to test that hypothesis with the latest genetic technology.

Morowitz was drawn from surgery to microbiology after witnessing the damage caused by a frightening infant disease: neonatal necrotizing enterocolitis (NEC). Seen often in premature babies, NEC causes intestinal inflammation that can require surgical removal and may lead to lifelong complications or death. As the surgeon on such procedures, Morowitz said he became interested in ongoing research on how to reduce the number of NEC cases.

“You say to yourself, ‘How can you prevent it?’ The literature tells you there aren’t many ways other than supporting breast milk usage,” Morowitz said. Others had proposed a link between breast milk, gut bacteria, and protection against NEC, but until recently the technology did not exist to take a full census of the microbial world, he said.

For the PLoS ONE paper, Morowitz and his team decided to study the effects of breast-milk versus formula on the microbe population in the intestines of piglets. By recording a “transcriptome” - a snapshot of gene expression - from the intestinal fluid of the piglets, Morowitz’s team could detect which bacterial species were present and active in the two groups.

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Chronic Fatigue Syndrome (CFS) is known as a “diagnosis of exclusion,” a disease with non-specific symptoms that can only be considered when all other reasonable diseases have been ruled out. Because there are no known proven causes of CFS, it’s impossible to design a test for the disease, and there is no defined treatment strategy. And yet, the CDC estimates that more than one million Americans have CFS, and patient groups are desperate for research into the origins of the disease.

Medical desperation begets controversy, and that’s what kicked up again this week with the publication Tuesday of a second report linking CFS to a mouse retrovirus. The research - which found DNA from the murine leukemia virus (MLV) family in more than 86 percent of CFS patients vs. only 7 percent of controls - would be interesting in and of itself. But the paper is the latest salvo in a scientific battle that has raged in the last year over the connection between CFS and viruses, exposing the modern balance between the slow crawl of research and the urgent desire of patients for information in the Internet age.

The first paper to link CFS with a mouse retrovirus was published last year in Science, creating a stir in the media and hope for CFS patients hungry for an explanation and a cure. But several subsequent studies failed to replicate the original finding, leading many to question whether the original experiments had been contaminated by mouse DNA or were simply not conducted properly. The controversy moved beyond the battlefield of scientific journals when the study’s senior author, Judy Mikovits, began to aggressively push the link between the retrovirus and CFS and other diseases - a saga recapped in an article earlier this summer by our friend Trine Tsouderos at the Chicago Tribune.

The new article, published by scientists from the FDA, NIH, and Harvard, gives conditional support to Mikovits’ original findings, detecting similar (but not identical) viral DNA in blood samples from CFS patients. The new study’s methods, which included extreme measures to ensure that no mouse DNA contamination could occur, were praised by many in the field. But the stench of controversy remained, as the paper only came out after being delayed two months while the authors reassessed their findings in light of yet another paper that failed to detect virus. CFS patient groups, who had received leaked word of the positive findings, cried foul over the delay.

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