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!

Have you ever cheated on a test by glancing over at someone else’s work? Or relied on a fellow student to carry the load on a group project while you coast along with minimal effort? While few will admit to these forms of cheating, they have long been fixtures of the classroom. However, a lazy individual benefiting from the hard work of a colleague is not a trick exclusive to humans. In a recent study of bacterial infections in plants, the laboratory of evolutionary biologist Joy Bergelson demonstrated that these unsavory practices can also be found in pathogens - and that may be a good thing for us.

In the bacterial world, the goal is survival. What we perceive as an infection is merely colonization for the bacterial population, who are establishing a new home where they can happily feed off the host’s nutrients and reproduce. Bacteria build and release virulence factors to achieve this settlement and evade immune system defenses. But because these factors spread out, benefiting an individual bacterium’s neighbors as well as itself, a sneaky bacterium can get by without producing its own virulence factors. In laboratory dish experiments, scientists observed that bacteria engineered without the ability to release factors can still thrive so long as they are paired with normal, pathogenic partners.

Though scientists described this “cooperator-cheater model” in the artificial environment of the dish, nobody had yet observed it in a natural setting. For a study published in September by the journal Ecology Letters, a team led by postdoctoral fellow Luke Barrett discovered the model in action within the cells of the popular genetic model plant Arabidopsis thaliana.

“We’re showing that cheating actually happens in nature, and that the cheaters persist,” Bergelson said. “You can make cheaters that do well in the lab, and you can show that these systems may be stable in theory, but to show that it is actually happening in nature is novel.”

Recently, researchers discovered that Arabidopsis carried two strains of the bacteria Pseudomonas syringae, a common plant pathogen. While one strain had all the normal pathogenic activity, another was a kind of bacterial pacifist, with a broken system for secreting virulence factors. Surprisingly, these two strains appear with almost equal frequency in Arabidopsis, suggesting that the non-pathogenic strains are far more successful in nature than previously thought.

To test the nature of this relationship, researchers took the two natural strains and experimentally infected plants with only one or the other. When grown alone, the “cheater” strain was not nearly as successful without its more aggressive partner around to unwittingly “donate” virulence factors. Additional modeling suggested that the more aggressive the virulent strain, the more likely it was that cheaters would be found nearby eager to exploit the hard work of their pathogenic peers. The cheater strains are also harder for the host immune system to spot, since the machinery that produces and releases virulence factors is a frequent target of those defenses.

“When you go into the field, it’s kind of a curiosity: why would non-pathogenic cheaters be almost as common as pathogens inside the host?” Bergelson said. “It turns out that the cheaters can do really well as long as they’re with the pathogenic variety, and they don’t pay the price of having to actually make a secretion system or effectors. They also don’t run any risk of being recognized because it is the presence of secreted effectors that causes the recognition events in the first place. So, these non-pathogens have some good things going for them.”

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If you are an avid reader of food packaging materials or a parent of an elementary school student, you might get the feeling that food allergies are on the rise. Statistics back up this notion, with the CDC reporting an 18 percent increase [pdf] in child food allergies between 1997 or 2007. That puts current estimates of food allergy prevalence at 4 percent for children and 2 percent for adults, with allergies to peanuts (3.3 million Americans) and shellfish (6.9 million) leading the way.

The factors driving this surge remain a scientific mystery, and answers are even more scarce when it comes to treating or preventing dangerous allergic reactions. Currently, the only way to prevent anaphylaxis caused by a food allergy is avoidance, a strategy that can be very cumbersome for parents raising small children who cannot be exposed to basic food groups. Dave and Denise Bunning faced this challenge with their two children, both of whom were allergic to milk and eggs, leading to “several emergency room visits before the age of 5,” Dave Bunning said. Those experiences inspired the family’s philanthropy for research into the science of food allergies, which included this year’s founding of the Bunning Food Allergy Professorship at the University of Chicago Medical Center.

At the official naming ceremony for the new position, the inaugural Bunning Food Allergy Professor Cathryn Nagler presented her latest research to a large crowd including the Bunning family themselves. Nagler’s intriguing theory about food allergies looks within, at the bacterial universes that exist inside the human body. In parallel with other laboratories on campus looking at the impact of the human “microbiome” upon diseases such as inflammatory bowel disease and diabetes, Nagler is focused on the trillions of bacterial tenants that occupy each of our bodies.

“It’s becoming clear that we are outnumbered,” Nagler said. “There are 10 trillion human cells encoding 20,000 genes [in an individual], but 100 trillion bacterial cells encoding an estimated 2 to 20 million genes. So there are as many E. coli in each of our digestive tracts as there are people on Earth…and that’s not even one of the more popular species.”

All those bacteria, sometimes called the “commensal microbiota” to distinguish them from disease-causing pathogens, could play the environment role in the genes + environment recipe for food allergies. Many of the trappings of modern life, including high-fat diets, antibiotic treatments, and the use of baby formula instead of breastfeeding, can affect the census of our bacterial inhabitants. In food allergies, where the immune system mistakenly treats innocuous dietary proteins as harmful invaders, these microbiota changes might tip the balance towards over-sensitivity to components of peanuts or shrimp.

“An increase in disease prevalence in 10 to 15 years’ time can’t be explained by genetics, so there’s got to be other factors that are driving this increase in disease prevalence,” Nagler said. “All of these environmental variables lead to alterations of the commensal microbiota, which in genetically susceptible individuals could drive allergic responses to food and other antigens.”

To study this model, Nagler’s laboratory gave a long-term treatment of antibiotics to lab mice, finding that this prolonged exposure did indeed trigger an allergic response to peanuts. Using genetic identification methods, her group compared the gut microbiomes of mice treated with antibiotics versus mice who did not receive the drugs, finding several differences in the bacterial populations colonizing their digestive system. One bacterial family, called Clostridia, were reduced in the mice treated with antibiotics, while another was increased — suggesting that reducing or decreasing different species of bacteria might affect the chances of developing food allergy.

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By Meghan Sullivan

What is it about viruses that so easily captures our attention? With the teeth mostly taken out of bacterial infections by the advent of penicillin and parasites a rare and mostly exotic concern, viruses remain one nemesis that we often struggle to treat. Unlike complex bacteria and parasites, viruses are little more than genetic material wrapped up in a vessel designed to take its blue prints to the next host. Once in a host, viruses inject their genetic material into cells and take over the cellular machinery to carry out their lifecycles. Imagine terrorists sneaking into a Ford factory and using the assembly lines to crank out WMDs. Infected cells eventually die, but not before triggering immune responses (coughing, sneezing, etc) that aide their spread to the next host.

Taken starkly, viruses execute an elegant life cycle. If the aim of life is to pass on one’s genetic material, viruses have succeeded by reducing themselves to only genetic material, relying on other organisms for the messy business of replicating and spreading. The only way to make the process more streamlined would be to cut out the effort of budding, replicating, and finding its next host.

Which, it seems, viruses have also done.

Called human endogenous retroviruses (HERVs), some viruses have slipped their genetic material into our genome, inserting themselves between host genes or in the long stretches of inaptly named “junk” DNA. Over the course of evolution, these genetic stowaways were passed down to the host’s offspring right alongside genes for blue eyes and attached earlobes. Millions of years later, we find remnants of the viruses encountered by our ancestors written in our DNA like graffiti in a bathroom stall. HERVs comprise as much as 8% of the human genome and some may have integrated into our genomes as long ago as 60-70 million years ago.

Considering the vast changes our genome has undergone in the past 70 million years (by comparison, the human-chimpanzee split occurred only 6 million years ago) it makes sense that the HERVs fossilized in our genome have also been changing. HERVs, like the rest of our genome, acquire DNA mutations at a low but consistent rate. Scientists are able to estimate when a HERV integrated - and by extension, when it was last infectious - by comparing mutations in long terminal repeat (LTR) sequences, stretches of DNA that flank the viral genes like book ends. At the time of integration, these regions are identical, but the longer the HERV has been in the genome, the more mutations the LTRs acquire. By comparing the differences in LTRs flanking HERVs, scientists can estimate how long a HERV has been in the genome.

Previously, the youngest HERVs were estimated to be 800,000 years old. For a recent paper in the journal PLoS ONE that explored how recently HERVs were actually circulating as viruses, Aashish Jha, a University of Chicago graduate student in the Department of Human Genetics and former member of Douglas Nixon’s lab at UCSF, looked for recent integrations into the human genome. Using a genome browser at UCSC, Jha and colleagues tracked all the human-specific, full-length HERVs at a particular place in the human genome. Interestingly, one HERV called k106 didn’t fit the normal timeline.

“It looked interesting because it did not have any mutations in its LTRs,” Jha said.

This was an unusual find, as the age of most HERVs insures at least a few mutations that would aid in dating it. Using genetic information from 51 ethnically diverse individuals, Jha and colleagues were able to estimate that the k106 HERV integrated between 92 and 100 thousand years ago, making it one of the youngest HERVs ever identified.

“This time period is exactly the time modern humans were emerging,” Jha pointed out, “So someone was infected and, given that it was a small population size, it rapidly became fixed in the genome. Then humans moved out of Africa…so even though the virus is new we find it fixed in every human population.”

Having identified this recently integrated, human-specific HERV, it’s possible to gain insight on the ways HERVs have affected the course of our development. LTRs flanking HERVs contain signals that control when and where genes are turned on and off. Placing these viral signals in front of host genes could impact how and when they are expressed and, in some cases, lend an advantage to the individuals possessing it.

“There are multiple ways they [affect evolution],” Jha said.

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Actin is the Lego of the cell. The small proteins can be assembled into many different forms for a wide variety of uses: serving as a scaffold to keep the cell’s shape, a railroad for shipping packages, or a powerful motor to propel the cell or tear it in half. But actin itself is a blank slate, an interchangeable material that needs guidance to do anything more than stick together in chains called filaments. To truly understand the Lego of the cell, you have to understand the factors that prompt it to form into its many useful conformations.

“The actin itself is boring. It’s just a building block,” said David Kovar, assistant professor of cell & molecular biology and molecular biophysics at the University of Chicago. “These filaments have to be assembled at the right time and place, they have to be organized with the right architecture, and the dynamics have to be correct - some structures are assembled and stable for minutes to hours, whereas others are assembled and disassembled on the order of seconds.”

Kovar’s lab studies actin-binding proteins, the cellular tools that shape formless actin into functional filaments. This area of research has exploded as scientists discovered multiple actin-binding proteins, each with their own unique properties. One element, the actin-related protein 2/3 complex (Arp2/3 for short), creates branches in the normally linear filaments. Another, called formin, attaches to the end of the filament and steps on the gas, causing it to grow at an accelerated rate.

Scientists have learned a lot about actin engineering by using a method called TIRF microscopy, which allows them to watch as actin filaments form, grow, and take shape. [A short video of Arp2/3-induced branching is available below.]

“This enables us to actually watch these things in real time, and it has revolutionized the field,” Kovar said.

In a new paper, published last week in the journal Nature Structural & Molecular Biology, Kovar’s laboratory and collaborators at the University of Pennsylvania eavesdropped on the activity of a newly-discovered class of actin-binding proteins, named for a shared feature called the WH2 domain. By studying one such WH2 domain protein, isolated from a water-dwelling bacteria that causes gastrointestinal problems in humans, the lab found themselves watching a new, chaotic kind of actin-forming behavior - akin to how a toddler might choose to play with Legos.

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Writing about science means looking up a lot of numbers. Trying to find a figure for the number of cells in the body or the protein-encoding genes in human DNA or patients diagnosed with ovarian cancer from 1980 through 1995 can eat up a lot of time and internet bandwidth. For some of these oft-cited numbers, there’s a mutually agreed upon estimate that science writers can drop into the articles, such as the 23,000 usually tossed around for the number of human genes. But it’s worth remembering that these figures are subject to change - after all, it was thought as recently as 10 years ago that there were 100,000 genes in human DNA.

A new counting kerfuffle broke out this week for yet another oft-cited scientific figure: the number of species on Earth. Last year, zoologist Robert May proposed in Science that the human race would be “embarrassed” should aliens show up tomorrow and ask how many different types of organisms live on our planet. Depending on the model used, one could argue for a number anywhere between 3 and 100 million eukaryotes, May wrote - and that doesn’t even count viruses and bacteria, which far outnumber the larger species.

But as the authors of the PLoS Biology article “How Many Species Are There on Earth and in the Ocean?” found out this week, picking a number within that range is hazardous territory. Using a mathematical model based on the roughly 1.2 million species we currently know about, the research team calculated a new estimate: approximately 8.7 million species from land and sea. Of those, only 14% of land species and 9% of sea species have so far been cataloged by humans, the authors concluded, and describing those remaining could take over 1,000 years and $364 billion. “Our results also suggest that this slow advance in the description of species will lead to species becoming extinct before we know they even existed,” they wrote.

Dramatic stuff, but what about the math? In Carl Zimmer’s article on the study for the New York Times, the first bubbles of discontent can be felt around the biology world, from fungi experts to entomologists who argue that the 8.7 million number is far too low. Scientists who study microbes were even less pleased with the mathematical model, which they said dramatically under-counted their favorite species. On his blog, Phylogenomics, microbiologist Jonathan Eisen pish-poshed the paper’s estimates of 10,000 prokaryote species: “I think without a doubt the number of bacterial and archaeal species on the planet is in the range of millions upon millions upon millions.  10,000 is clearly not even close.” Two other microbiologists wrote a letter to the Washington Post, pointing out that “a teaspoon of soil contains more than 10,000 species of bacteria.” For the time being, it looks like our alien visitors will have to be satisfied with the answer, “Lots.”

Elsewhere…

Speaking of the importance of bacteria and microbes, consider the discovery of antibiotic-resistance genes in 30,000-year-old bacteria from the Yukon Territory. Though these bacteria lived approximately 29,930 years before the discovery of penicillin, they possessed defenses against the naturally-occurring weapons scientists have seized upon to develop infection-fighting drugs. That long history means outsmarting drug-resistant bacteria may be even harder than scientists thought, and makes the case for even more selective use of antibiotics. “Bacteria share these genes like baseball cards with each other,” Stuart Levy at Tufts University told Nicholas Wade of the New York Times.

Has an important culprit in amyotrophic lateral sclerosis, aka Lou Gehrig’s disease, been discovered? The Medical Center’s Raymond Roos comments on a recent Northwestern University study.

On the blog, we’ve covered the link between sleep loss and testosterone, weight gain, and blood sugar. A new study from UCSD and Harvard now finds a connection between sleep quality and blood pressure. Our sleep research guru Eve Van Cauter commented on the research for TIME.

Just another reminder to check out the Medical Center’s new Facebook page, where this week you can find articles from the blog, information on the DNA Discovery Lab at the Field Museum, and President Sharon O’Keefe’s letter to the editor on hospital charity care. If you like it, please hit that “like” button!

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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By John Easton

At 1:30 pm, on Monday, December 12, at its Annual Meeting and Exposition in San Diego, The American Society of Hematology will recognize Janet Rowley of the University of Chicago Medical Center, and Brian Druker of Oregon Health & Science University, with the 2011 Ernest Beutler Lecture and Prize for their significant advances in the diagnosis and treatment of chronic myeloid leukemia (CML), a cancer of the blood characterized by an overproduction of white blood cells.

This is a great honor - and a storage problem.

Rowley has received many prizes over the course of her career: the Lasker Award, the Gruber Genetics Prize and the American Association for Cancer Research Award for Lifetime Achievement. President Jimmy Carter appointed her to the National Cancer Advisory Board. President Bill Clinton awarded her the National Medal of Science. George W. Bush selected her for his President’s Council on Bioethics. She stood with President Barack Obama when he signed the stem cell research bill and she returned to the Obama White to accept the Presidential Medal of Freedom. Then she moved to a new office with a better view, but less shelf space.

Rowley has long been known for brilliant insights, intellectual rigor, and relentless tenacity, but never for extreme neatness. “Her filing system involved piles,” said MaryBeth Neilly, a senior research technician who works with her. When preparing for the move, “we found awards all over the place,” she said. “We knew we needed a place to put them, and that her office was not that place.”

Thus was born the shrine. “Once we moved, but before we unpacked, we ordered a display case,” said Neilly. She and Rowley sorted through the honors and picked the cream of the crop; those that were the most significant, or that looked really cool. Lots of them, some of the trophies, most of the plaques and the vast majority of honorary doctorates, were transported - lovingly, but in bulk - to the University archives.

The display case soon filled to capacity. “There’s a lot of crystal in there, a lot of shiny metal,” Neilly said, such as the National Cancer Institute’s Rosalind E. Franklin Award for Women in Cancer Research, a big carved glass bowl, or the National Medal of Science, a golden medallion.

A few favorites - for reasons aesthetic or sentimental - wound up in Rowley’s office, including the Lasker, the Presidential Medal of Freedom, a large, twisting crystal chromosome from the Jeffrey M. Trent Lectureship in Cancer Research, and a bronze sculpture from the Leukemia and Lymphoma Society. A few more are at Rowley’s house. Two made of a particularly valuable soft, shiny heavy metal, stay at a local bank. The exact positioning of the Beutler Prize has not yet been determined.

Elsewhere…

Vijay S. Dayal, a longtime fixture of the Medical Center’s otolaryngology department, passed away last week at the age of 74. A head-and-neck surgeon and expert on hearing and balance, Dayal was also known as a skilled inventor, obtaining patents for an artificial voice box and a customized “rotating chair” used to test dizziness and balance. “Testing in the chair is not uncomfortable for the patient,” Dayal said in 1991. “It’s like a mild ride on a merry-go-round and it provides us with information we cannot get any other way.” You can read another obituary for Dr. Dayal at the Chicago Tribune.

What’s it like to be a medical student? Pritzker first-year Akash Parekh narrates a day in his life for US News & World Report. Spoiler alert: there’s not much free time, or sleep.

If parents refuse vaccinations for their child, should pediatricians be allowed to refuse to take them as a patient? That interesting ethical question was the subject of an article by the Chicago Tribune’s Deborah Shelton.

The new Scientific American blog network officially launched this week, and provides a new home to many of my favorite science bloggers. For a taste, check out Lucas Brouwers’ post on the evolution of E. coli, and this interview with John Boswell of Symphony of Science (best known for the Carl Sagan autotune track “A Glorious Dawn”).

The latest cult favorite in the sphere of human genetics is the microbiome, the genes of the bacterial species that live inside and upon the human body. Because bacterial cells outnumber human cells in an adult by approximately ten to one, and tens of thousands of different species make up the human ecosystem, studying this world will be even more of a challenge than the Human Genome Project, which only had to concern itself with a single species: us. But as the microbiome is increasingly discovered to play a role in obesity, diabetes, infant diseases, and hospital-acquired infections, the number of researchers pondering a bacterial angle for their own disease of interest is exploding.

So the microbiome was the ideal topic for the first lecture of the Institute for Translational Medicine seminar series on Advanced Tools, a monthly meeting designed for University of Chicago researchers to share methodological know-how. Leading the discussion was a veteran of the young microbiome scene - Eugene Chang, professor of medicine and an expert on gastroenterology. For several years, Chang has applied the tools of microbiology to the bacterial populations of the human gut, looking for mechanisms involved in digestive diseases. As the techniques for studying the microbiome have evolved, Chang said he has seen the pros and cons of the field’s growth.

“This is an area that is really hot,” Chang said. “It isn’t coincidental that this interest has coincided with emerging technologies, because the emerging technologies over the last decade have allowed us to look at the microbiome in many different ways….but this is a field where you can be easily consumed by the technology.”

Those techniques have changed alongside the trends of the broader field of microbiology, Chang said. Scientists interested in bacteria were once limited to studying what they could both find and grow in a lab dish, which left the vast majority of species unexplored. But new genetic techniques have brought those hidden worlds into the light, allowing scientists to take a more complete census of the bacteria present in a given sample from the Earth’s environment, or the special environments within the human body. With this added power has come a whole new menu of choices for scientists, from low-cost methods (i.e. T-RFLP) that can take a surface-level snapshot of the most common members of a microbial community to deeper sequencing that can identify rare microbes that may turn out to be relevant to disease (i.e. pyrosequencing).

“We have a number of techniques that have advantages and limitations,” Chang said. “What you use is dependent on what your question is and how deep you need to go.”

In Chang’s laboratory, the questions relate to the origins of inflammatory bowel diseases such as ulcerative colitis. A recent study looked at the microbial diversity within the colon, comparing the bacterial populations present in the mucosa of the proximal colon (near the small intestine) to the distal colon (near the anus). A T-RFLP analysis, which looks at fragments of ribosomal DNA in the mucosal samples, found that the microbes present in the two regions were distinct, with higher “richness” (the number of species present) observed in the proximal versus distal colon.

But to determine the role of the microbes in disease, just taking a census isn’t enough. The newest wave of microbiome research is focused on function, using techniques that find out what those billions of bacteria are actually doing inside our bodies or out in the world. With metagenomics, scientists can analyze all the genes from a given sample of soil, skin, or mucus, then group those genes by their functional role (metabolism, transport, etc.) using a technique developed by Argonne called MG-RAST. Many groups, including Chang’s team, are also interested in measuring host-microbe relationships - how the bacterial population affects the biology of their home organism.

“Sure we can say who’s there, but how do we actually know what’s important?,” Chang said.

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By John Easton

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

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

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

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

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

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

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

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

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

by Meghan Sullivan

It would be easy to mistake the images in Harry Noller’s presentation last Thursday for shards of gemstones or modern art. “This part of the talk was influenced by our visit to the Art Institute,” he quipped, advancing through a gallery of slides that showed off a variety of crystals, ranging in color and shape. This was not, however, a geology talk. Noller, professor of molecular cell & developmental biology at the University of California, Santa Cruz, was this year’s invited speaker for the 6th annual Haselkorn Lecture, a seminar series named for UChicago molecular biologist Robert Haselkorn that invites leading researchers to the University for several days to interact with young scientists. His visit drew to a close with a lecture on the molecule he’s spent most of his life studying, the ribosome.

Every living thing possesses ribosomes. It makes sense, then, that ribosomes are fundamentally necessary for life, and may predate proteins and even DNA in the history of life on Earth. Since the identification of DNA, an overarching rule of life has emerged called the Central Dogma, which states that an organism’s DNA is transcribed into RNA, which is then translated into proteins. It’s as if you’re copying instructions from a cookbook. The cookbook - in this case, DNA - holds all the recipes, and you can copy out only the individual recipe you need - the RNA. The copied recipe can then be used as a reference to make the final product, proteins. But as with cooking, you can’t simply turn words on a page into chocolate chip cookies. Like a baker might hold a recipe with one hand and mix the ingredients together with the other, the ribosome is the stepping stone between RNA and proteins.

“Going from DNA to RNA is something like going from Spanish to Portuguese - they’re similar types of molecules,” Noller pointed out, “But going from RNA to protein is like going from Portuguese to Chinese - they’re two totally unrelated languages. In this case, the ribosome is the Rosetta stone.”

The ribosome, which can be found in the fossil record going back 3.5 billion years, is a molecular machine that reads RNA and assembles the protein it encodes. Unlike many of our enzymes, it is composed mostly of RNA, not proteins. Its unusual composition and the fact that it lies at the heart of a process fundamental to life has made it a frequent subject of research.

Noller’s laboratory focuses on the structure and function of the ribosome. This is where the gallery of crystals comes in. Ribosomes, while relatively large cellular structures, are small enough that microscopy can’t provide the kind of detail necessary to understand the nuances of their structure. To get around this, scientists use a method called X-ray crystallography. In essence, Noller’s lab tries a variety of conditions to coax ribosomes into forming microscopic crystals, made up of repeating units, which forces the ribosomes to form symmetrical, 3D structures. At low power on the microscope, researchers can see angular crystals. However, when placed in the path of a X-ray, the crystal breaks up the X-ray beam into a complex scatter, which is caught and recorded. Using a mathematical operation called a Fourier transformation, the scatter of dots, each of which represents a single atom in the molecule, is resolved into a 3D model.

The problem with crystallography is that it only gives us a snapshot of its target. By forcing the ribosomes into crystals, they lose all ability to move. It’s well established that ribosomes, which must deal with growing proteins and move along the RNA, are dynamic molecules, moving and changing conformation as they work. Thus, still images don’t tell the whole story, a limitation Noller described with the parable of the cavemen and the Ferrari.

“The caveman and his cave-buddies are having beers and telling stories and they come out of the cave and see this.” Noller showed an image of a vintage Ferrari.

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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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Since the time of Linnaeus, scientists have loved classifying the world around them. But while centuries of biologists have worked to collect and categorize the plants and animals of Earth, all that work likely only covers about a minute fraction of our planet’s life. As much as 99 percent of the biodiversity on Earth is smaller than 2 microns - bacteria, viruses, and tiny eukaryotes - and most of these remain to be discovered by humans. There are more microbial cells on earth (1 nonillion, or 1×10^30) than there are stars in the sky, and all of this new life exists in soil, in seawater, and inside animals, plants, and even us.

“You are mostly microbes,” Jack Gilbert told the Institute for Genomics and Systems Biology in a lecture last month. “The world is mostly microbes, and yet we have less of an understanding of how microbes run the universe than we do of the universe itself.”

Gilbert, an assistant professor of evolution and ecology at the University of Chicago, is part of an international project to remedy that shortage of knowledge about the microbial world. The Earth Microbiome Project, a group bringing together scientists from several different institutions, is dedicated to filling in these gaps in the tree of life and, more importantly, figuring out how they may be secretly pulling the strings of Earth’s ecosystems. In his talk, Gilbert rapidly narrated the group’s aims and his own research projects until he ran out of breath, leading an hour-long tour around globe in search of nature’s smallest and most abundant participants.

Classically, microbiology has taken place in cell culture dishes and incubators, as scientists grew bacteria in the laboratory in order to study its identity and function. But the field has benefited greatly in recent years from genetic advances opening up new paths of discovery. As the price of accurately sequencing DNA and its products has exponentially dropped - driven largely by the demand for human genomics - ecologists interested in microbes have borrowed the technology for their own uses. Now, instead of growing bacterial populations in the laboratory, microbiologists can take a genetic sample of whatever environment they wish and use the genes in that sample to reconstruct its microbial denizens. This process is called “metagenomics,” and it is expanding our knowledge of the bacterial world in leaps and bounds, Gilbert said.

“We can take a sample, sequence it, look at the microbial taxa in there, and identify things we couldn’t culture,” Gilbert said. “There are four trillion base pairs of genetic information in a millileter of seawater, in one teaspoon. In a gram of soil, there are about 4 quadrillion base pairs.”

With so much information out there waiting to be discovered, one of the most important questions is where to start. The Earth Microbiome Project is overseeing dozens of projects, each with their own hypotheses and environmental targets. Gilbert outlined just a few: analyzing samples from near the site of the Gulf of Mexico oil spill; comparing soil samples - some as old as 135 years old - from China, France, Australia, and South America; characterizing the microbial communities from the vaginal canals of fertile and infertile pandas in the San Diego Zoo (seriously). Importantly, the procedures used to analyze such widely different samples are being standardized by the project to ensure that comparisons between different research groups and samples are possible.

“The goal of this project is to systematically approach the problem of characterizing microbial life on Earth,” Gilbert said. “We’re reaching a zenith point in our ability to do things individually, and if we want to start generating synthesis of our understandings, we need to start working as a team, as a group, like the physicists do. We want to do the same thing: Come together as a group and say ‘we have a really good idea, a life-changing idea that will change the way we live on this planet, we just need to do it in a systematic and well organized fashion.’”

As a discrete example, Gilbert offered one of his own research projects, conducted before he relocated to Argonne National Laboratory last summer. As senior scientist at Plymouth Marine Laboratory in England, Gilbert and his team studied a section of the English Channel that has been sampled by scientists every week since 1864 - interrupted only by the two World Wars. Since 2000, the team has taken samples suitable for metagenomic analysis, and has methodically characterized what microbes live in this patch of water and how that population changes.

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Alien Life & Scientific Skepticism: The Sequel

In a bit of deja vu this week, a new paper stirred up fevered online debate about the existence of aliens among us - and the traditions of scientific publications. This time, ground zero for the debate was not the bacteria of arsenic-laced Mono Lake, but microscopic filaments on a rare group of meteorites collected in Antarctica in the 80’s and 90’s. In a paper published last Friday by the Journal of Cosmology, NASA scientist Richard Hoover argued that these filaments are bacterial fossils, of species that fell to Earth with the meteorite - a conclusion that was breathlessly reported by Fox News with the lede “We are not alone in the universe.”

Panspermia, the idea that life on Earth may have been seeded by alien organisms that arrived on the backs of meteorites, is a seductive idea. But as the old saying goes: once bitten by reports of alien bacteria, twice shy. Far fewer science reporters fell for the meteorite alien bacteria as they had on the arsenic-based bacteria story of last December, perhaps because of a lesson learned or merely because of the lower-profile journal in which the new paper appeared. And while the criticisms over the arsenic study took a few days to seep from science blogs to mainstream media, the travel time was much shorter this time around - Phil Plait’s skepticism on his Bad Astronomer blog was quickly trailed by an AP story that carried a chorus of criticism. Questions about the qualifications and objectivity of the author and the journal soon followed, as the Columbia Journalism Review recaps.

As with the arsenic story, the meteorite episode was almost more fascinating for what it says about modern scientific communication than what it said about science itself. On the surface, the Journal of Cosmology appeared to take some progressive steps for publishing research, including making the article free and open access and soliciting commentaries from “100 experts” on the findings, 24 of which were published soon after the original article. That move would appear to address one of the critiques of the team that published the arsenic bacteria paper, regarding their attitude that criticism was only valid through traditional (and slow) peer-reviewed channels, instead of online discussion that is able to react more immediately.

However, a very thorough, critical commentary by microbiologist Rosie Redfield (who also sounded the first alarm about the arsenic bacteria research) has not been published by the journal, while some very odd commentaries have, such as one concluding “Hoover’s findings are incompatible with the creationist model of life based on biblical Genesis and Aristotelian philosophy.” The journal has also reacted petulantly to criticism, posting an editorial called “Have the terrorists won?” that claims “Only a few crackpots and charlatans have denounced the Hoover study.” So while the latest alien bacterial invasion of Earth’s media is showing some steps in the right direction, it also signals that the growing pains of adapting scientific discussion to a faster media age are still present.

Elsewhere…

Last week, the Medical Center was part of a four-way kidney swap that spanned the country, from the Bronx to California (we should have a video of the event posted next week). Coincidentally, in a New York Times editorial published Sunday, the Medical Center’s Lainie Ross argued that such swaps or “donor chains” were a better option than proposed revisions to the current organ allocation system that would prioritize younger recipients.

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An elephant fish embryo and its yolk (courtesy Andrew Gillis)

Billions of years of evolution has produced an incredible diversity of life - “endless forms most beautiful and wonderful,” as Darwin famously put it. But a fascinating thing about evolution is it has produced such a wide variety of species with a relatively small amount of tools. Many of the roughly 23,000 human genes can be found in species as different as mice and flies, and those genes control embryonic processes that are remarkably similar despite the vastly different outcomes for an insect or a man. But sometimes, finding out just how deep this homology runs requires deep exploration.

Members of Neil Shubin’s laboratory are no strangers to adventure. The search for Tiktaalik, the famous fossil of a transitional species between fish and land-dwellers, took Shubin and his collaborators to remote stretches of the Canadian Arctic. So when J. Andrew Gillis, then a graduate student in Shubin’s laboratory, wanted to study an obscure aquatic relative of sharks with famously hard to acquire eggs, the evolutionary biologist could hardly turn him down.

“I remember when Andrew said ‘I want to get some holocephalans in the lab,’ and I thought ‘yeah, right.’ Everybody’s tried this for years; there’s a long line of people who have always wanted to get holocephalans in the laboratory,” said Shubin, the Robert R. Bensley Professor of organismal biology and anatomy at the University of Chicago. “It’s not like you can buy them at a store, it’s not like you can breed them easily in a lab. They breed on the bottom of the ocean, so you have to find places where the eggs are accessible.”

Holocephalan eggs are prized by evolutionary biologists because of a small but significant anatomical difference from their cousins, the sharks. Both share skeletons made of cartilage and other structural features, but split in terms of appendages called branchial rays, structures that grow outward from the skeletons’ central gill arches. While sharks form several sets of these rays, holocephalans only grow a single set near their head, which eventually forms the support for gill covers. Finding the genetic switch that triggers this anatomical difference, as Gillis, Shubin and colleagues did in a PNAS paper published yesterday, would shed light on the origins of appendage development across the animal kingdom, from fins to wings to limbs.

But first, a scientist needs to leave the safe world of their laboratory in order to find those precious eggs. Gillis’ quest for the embryos of the holocephalan species elephant fish, named for their prominent snout, led him halfway around the world and under the water, on SCUBA expeditions in Australia and New Zealand. Based on anecdotal information collected from local fisherman and marine biologists, Gillis was able to score a precious few eggs to take back to the laboratory for his experiments - but it wasn’t easy.

“Diving for elephant fish eggs was not always a pleasure trip,” said Gillis, now a postdoctoral researcher at the University of Cambridge. “Unfortunately, elephant fish like to lay their eggs in cold, muddy, shark-infested bays, so we spent months seeking out sites like this in southeastern Australia and New Zealand. When you finally find a few eggs in the muck, it feels like winning the lottery.”

Back in the comfort of the laboratory, the mood was still tense, as Gillis had to get all of his experiments working just right so as not to waste the valuable cargo from his expeditions. Previous work by Gillis and Shubin discovered that shark embryos use a gene called sonic hedgehog (Shh) to control the development of branchial arches. The next step was to test whether elephant fish embryos also use this genetic switch to mediate the growth of their less robust appendages.

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