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!

The 2009 H1N1 pandemic, better known as the season of swine flu, was not like other flu seasons of recent vintage. A typical seasonal strain of influenza is most deadly at the extremities of age, with the highest mortality rates in the very young and very old. One of the reasons why experts were concerned about the 2009 flu was that it went off-script, killing mostly people in their twenties and thirties. Influenza researchers speculated on why the normally vulnerable elderly appeared to have the advantage against this particular pandemic. But it wasn’t until a recent study by University of Chicago and Stanford scientists looking at the failure of flu vaccines in older adults that the source of this advantage revealed itself.

In a typical season, senior citizens are among the priority groups for receiving the flu vaccine, due to their increased risk of severe symptoms. Yet the success rate of the standard influenza vaccine is reduced in those above 65 years of age, falling from 90 percent efficacy to as low as 17 percent. Most have attributed this decline to a general principle called “immunosenescence,” the weakening of a person’s immune system as they grow older. Since vaccines work by stimulating the production of antibodies against an inactivated flu strain to protect against the real virus, is the deficiency in the aged a matter of antibody quantity, quality, or both?

A multi-institutional team led by co-first authors Meghan Sullivan of UChicago and Sanae Sasaki of Stanford developed a new assay to test this question for a recent article in The Journal of Clinical Investigation. Two groups of volunteers - one aged 18-30, one aged 70-100 - received the seasonal flu vaccine in the winter of 2007-08, and researchers took blood samples from them seven days later, when vaccine-induced antibody production is at its peak. Scientists could then measure the number of antibody-secreting cells, called plasmablasts, and antibodies circulating in the blood of the volunteers. They could also run experiments testing how well those immune defenses bind different strains of influenza, the first step in fighting off a virus.

Their first experiments replicated the clinical data - even in a test tube, younger volunteers (or at least their antibodies) are much more likely to respond to the influenza strains included in the vaccine than samples from older subjects. Subsequent experiments revealed that the immune systems of elderly subjects were at a numerical disadvantage, with significantly fewer plasmablasts observed in serum compared to the samples from their younger counterparts.

“It had been appreciated before that there are fewer immune cells in older people, but this is the first time showing that fewer antibody secreting cells are raised in response to vaccination,” said Sullivan, a graduate student in the laboratory of Patrick Wilson (and a contributor to ScienceLife).

But surprisingly, that was where the immune deficits in older patients started and ended. Though there were fewer plasmablasts in older subjects, each produced the same number of antibodies as those of the young. What’s more, when the antibodies from young and old were compared for their ability to bind the viral strains targeted by the vaccine, they were nearly identical. So the failure rate of vaccines in elderly can be explained by the lower quantity of antibody “factories,” rather than a defect in the quality of the antibodies themselves.

“We would think that antibody activity would be decreased in older people, but in fact the ability to bind is basically identical,” Sullivan said. “The antibody secreting cells are the weak point; elderly people are just not making enough.”

Amid the media storm surrounding the rapid spread of swine flu in 2009, the research team used the same samples to test another idea. One theory for why senior citizens were protected against that particular H1N1 strain was that they may have been exposed to a similar influenza that circulated before 1950. With their blood samples, the researchers could compare how the antibodies of their old and young subjects responded to the 2009 H1N1, which neither group had been vaccinated against two years prior. In this competition, the senior citizens were the surprise winners - antibodies from older subjects (especially those older than 78) were more responsive to the H1N1 virus than those from younger volunteers.

The result suggests something off an immune system trade-off in the elderly. Though they may have a harder time producing sufficient antibodies to fight off the flu, the antibodies they do produce are able to attack a more diverse range of influenza strains.

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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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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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It’s fair to say that vaccines haven’t had the best few years in terms of PR. The “anti-vax” movement of parents suspicious about potential side effects of childhood vaccines has grown in strength, despite numerous studies proving their fears to be foundless. Certain high-profile diseases, such as HIV, have repeatedly proven resistant to traditional vaccine approaches. Meanwhile, vaccines suffer somewhat from their own incredible success - with many of the diseases that once caused rampant child mortality now under control or eradicated, one might think that the tool has maxed out its potential.

But two talks on Wednesday at the University of Chicago suggested that the age of vaccines is far from over. A revolution in the scientific approach to creating vaccines has begun to yield promising new strategies for controlling previously stubborn diseases, such as meningococcus and MRSA. Those advances have also made vaccines safer than ever, eliminating even the small risk inherent in the vaccines used early in the 20th century. As scientists move on to tackling diseases of adolescence, adulthood and developing countries, the ability of vaccines to change the world is only growing, said Rino Rappuoli, global head of vaccines research at Novartis Vaccines and Diagnostics.

“Most people say the last century of vaccines has been very positive: they eliminated polio, they eliminated diptheria and tetanus - what are you going to now, are you out of a job?,” said Rappuoli, who delivered the 2010 George & Marie Andros Lecture.  “But I believe, in the 21st century, vaccines are going to be as important, and maybe more important, than they were in the 20th century.”

Until the late 1970’s, Rappuoli said, the strategy for creating new vaccines was largely the same as the approach developed by Louis Pasteur nearly one hundred years prior: Isolate, Inactivate, Inject. Pasteur learned that exposing a person to a non-toxic version of a disease-causing bacterium or virus sensitized their immune system, such that subsequent exposures to the true pathogen were fought off. That strategy led to vaccines for smallpox, measles, diptheria, mumps, polio and many other diseases that were once a scourge upon young children.

Nevertheless, several diseases remained unpreventable with this traditional vaccine approach, frustrating the field. Then, like many other scientific areas, new hope arrived in the form of genomics, which made a new form of vaccine research possible, Rappuoli said. With genomics, scientists developed reverse vaccinology, the process of sequencing a bacterial or viral genome to find components of the pathogen that are promising as “protective antigens” in a vaccine. Rappuoli discussed the first success of this method - the creation of a vaccine for meningococcus, which was given to all children under the age of 18 in the UK in 2000.

“The genome approach and the biology approach combine together and very frequently can bring you to a new, potential vaccine,” Rappuoli said. “These things were not possible before the genome. It would have taken one scientist a lifetime to develop.”

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Bill Gates walks across the University of Chicago campus April 20, 2010. (Photo by Jason Smith)

A College Dropout Returns to Campus

The per capita income of Hyde Park experienced a brief spike on Tuesday as Microsoft founder/billionaire philanthropist Bill Gates paid a campus visit as part of his three-day college tour. After meeting with students and professors - including a walk-and-chat with Kevin White, pictured at left - Gates spoke and answered questions in a building named for another ultra-wealthy benefactor, the Rockefeller Chapel.

As Gates’ first college tour since resigning from Microsoft to focus full-time on his Bill & Melinda Gates Foundation, the focus was less on technology and more on the humble task of solving the world’s problems. With only a limited amount of time to speak, Gates focused on two priority areas for his foundation: child mortality and education. On the former point, Gates highlighted the vast differences between the wealthy world and the poor world in childhood death rates, with less than one percent of children dying before the age of 5 in rich countries while the death rate for young children remains around 20 percent in the third world. Vaccines are a big part of that change, Gates argued, which is why his foundation recently sunk another $10 billion into vaccination efforts around the world.

Interestingly, Gates said he once worried whether reducing infant mortality in developing countries could lead to more problems in terms of overpopulation and resource scarcity. But in fact, Gates said, studies have found that better health leads to smaller families, as parents choose to have fewer children when the chances of them living to adulthood increases.

You can find more coverage of Gates’ visit at the University of Chicago News Office.

A Year of Swine Flu

Hard to believe it was only one year ago that the world first learned to be afraid of the collection of letters and numbers known as H1N1. As a newspaper reporter at the time, I recall being impressed by the speed of the outbreak - not the virus outbreak, mind you, but the outbreak of media hysteria over the virus. For sure, there was reason to be alarmed about the novel H1N1 influenza, especially in the early days when the epidemiology was sketchy at best and seemed full of dire warning signs. But the leap from “new mysterious flu strain” to “1918 Pandemic Redux!!!” happened almost overnight, and spread far more quickly than the actual virus. I found myself writing “calm down, everybody” articles almost from the time I was put on the story, as the flu experts I interviewed balanced their concerns with a healthy dose of scientific skepticism.

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An African Pygmy Kingfisher (Ispidina picta) from the Malawi expedition. (photo by Jason Weckstein)

The scenario played out last spring when “swine flu” suddenly became a household name. As public health agencies sprung emergency policies into place, scientists set about tracing the new H1N1 virus back to its source, following it from person to person and eventually to the animals where it originated. Understanding how the virus’ genes mutated in pigs could help scientists determine how it jumped to humans, and give clues as to the most effective ways to fight the disease. But in the time it took to reconstruct the origins of swine flu, thousands and thousands of people were were newly infected with the virus.

Fortunately, last year’s novel H1N1 virus ended up fizzling out into a run-of-the-mill flu - still deadly in a small percentage of people, but not the runaway killer it threatened to be in its earliest days. But we might not be so lucky with the next disease to jump from animals to humans, so monitoring potential threats before they crossover is a scientific priority. While the genetic sequences of more and more organisms are cataloged every day, the viruses, bacteria and parasites those organisms living inside those animals have barely been characterized.

That knowledge gap is the target of the Emerging Pathogens Project, a collaboration between scientists at the University of Chicago and the Field Museum announced Tuesday morning at the museum’s very cool DNA Discovery Center. Blending the centuries-old practice of gathering animal specimens on field expeditions and the bleeding-edge technology of large-scale genomics, the project hopes to give scientists advance warning and knowledge about tomorrow’s epidemics.

“We plan to treat each one of these animals as an ecosystem in and of itself,” said Shannon Hackett, head of the bird division at the Field Museum and co-leader of the project. “We’re really interested in what lives in and on these organisms.”

Those animal ecosystems were collected during an expedition last fall in the African country of Malawi, a trip that brought back roughly 1,100 bird and mammal specimens. A sampling of those (pictured above) were on display at the announcement of the project; just one shelf from the tens of thousands that store critters of all types in the museum’s vast collection facilities. In categorizing those specimens, the museum has moved increasingly to genetic analysis, but the Emerging Pathogens Project brings those efforts to a much larger scale.

That’s possible thanks to the genomics infrastructure established by Kevin White, director of the University’s Institute of Genomics and Systems Biology and Hackett’s leadership partner in the Emerging Pathogens Project. Having previously launched massive projects to study genetic regulation and the genetic makeup of tumors, White said there was still time to take on another scientific challenge. Gesturing at the DNA laboratory that was the backdrop for Tuesday’s event, White aid that the high-throughput sequencing technology now available could do an amount of work equivalent to several million of such labs.

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Here’s Part 2 of our conversation with Kenneth Alexander, M.D., chief of pediatric infectious diseases. In this second and last installment, we discuss what ordinary people can do to avoid getting or spreading swine flu, some steps that medical professionals can take, and what would constitute a flu pandemic.

Here’s a video we shot yesterday of Kenneth Alexander, M.D., chief of pediatric infectious diseases, answering common questions about swine flu.

The news of unusual swine flu cases in Mexico and the American southwest has raised concerns that the outbreaks could herald a new flu pandemic - though the anxiety level in this AP story on today’s news seems just a bit too high at this stage. Something about the tone smacks of that movie “The Andromeda Strain” - “it’s something we’ve never seen before…”

It’s important to be vigilant, but overreaction also can have costs. In 1976, the CDC instituted an emergency immunization program in response to an outbreak of swine flu. The vaccine they used may or may not have been the cause of an uptick that year in cases of Guillain-Barre Syndrome (see this for an account of the 1976 experience by the former directors of the CDC and the immunization program).

President Obama has a history of interest in flu pandemic preparedness. He co-wrote a 2005 op-ed in the New York Times on pandemic measures, and later that year I interviewed him on that subject for the Chicago Tribune. You can see the transcript here. Two passages from that interview may offer clues about how Obama’s administration will handle the latest outbreak: 

Even when the SARS scare struck, the losses were in multiple billions of dollars. And that proved to be a false alarm essentially. If something like this genuinely occurred, you’d see global trade come to a standstill. And in addition to obviously the loss of life, the breakdown of our health systems, the economic consequences would be huge.

…you hate to be Chicken Little on this thing - no pun intended. But this is actually one of those situations where getting people a little scared, and certainly getting our government a little scared is probably a useful thing. And as I said, whatever investments we make are not going to be wasted, because the likelihood of pandemic is so high, even if it isn’t this particular pandemic. 

Perhaps Obama will see the issue differently as president than he did as a senator. But his instincts seem similar to those of the people who ran the 1976 immunization program - “When lives are at stake, it is better to err on the side of overreaction than underreaction.” If this outbreak continues, we may see another test of that idea.