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.

Racial health disparities in the United States have been repeatedly measured, demonstrated, and presented to the point where their existence is no longer in question. But still up for discussion is how to fix them, whether through sweeping legislation like this year’s federal health care reform, local efforts to improve health care access or social determinants of poor health, and/or by customizing care to better serve minority populations. But what about that time-honored American way of dealing with injustice and unfairness - why not tell disparities “I’ll see you in court!”?

The idea is not so far-fetched, said Anup Malani, a professor of law and medicine at the University of Chicago, in his lecture to the MacLean Center for Clinical Medical Ethics in early December. After all, the Civil Rights Act of 1964 was created to address segregation and inequality in schools, employment, and other important aspects of life, so why not medicine? History shows that Title VI of the Civil Rights Act, which forbids racial discrimination by any body that receives federal funds, was one of the most effective strategies ever in reducing racial health gaps. After its passage, hospitals and other medical providers (nearly all of whom receive federal funding in the form of Medicare/Medicaid), could no longer legally segregate patients into different wards or treat them with different personnel. The result was a rapid improvement of health care for black populations, and a brisk narrowing of the disparity in measures such as infant mortality, Malani said.

“It was a huge, huge success,” Malani said. “We spend a lot of time in law school thinking about the great civil rights successes in education, and we’re studying the wrong thing. In four months, you got 1,000 hospitals to integrate. This is unbelievable…One would like to achieve that sort of result again.”

But the rapid integration of American hospitals in the 1960’s only reduced the gap, it didn’t eliminate it. Some hospitals also exploited a loophole in Title VI and simply moved to more affluent, predominantly white communities, a strategy that turned out to be difficult to litigate in Title VI court cases. Because hospitals could plead at least one legitimate reason for the move - usually the argument that they would no longer be financially viable in the inner city - the charges of civil rights violation were denied. Other limitations of civil rights cases, including federal limits on damages, high cost, slow pace, and inadequate penalties, also make Title VI the wrong weapon to use in fighting today’s racial disparities, Malani argued.

Those loopholes may have even created a major driver of health gaps, Malani’s research has found, in that a disproportionate number of minority (and poor) patients receive their treatment from the country’s worst-performing hospitals. This dynamic creates what Malani called a “between” disparity, where minorities receive care from lower-quality providers than white patients, rather than receiving poorer care from similar-quality providers. Statistics have supported that observation, showing that hospitals and ambulatory care centers that treat more minorities have lower scores on measures such as mortality.

Therefore, though it hurt Malani to admit it (”it’s awkward for me as a lawyer to say I’m not the solution,” he joked), the most effective strategy may not be litigation but policy efforts to help the low-performing hospitals. Improve the statistics of these health care providers, and you hopefully reduce the racial gap by reducing “between” disparities.

“Let’s send funds to these hospitals,” Malani said. “If you just target the worst hospitals in America, you’re going to disproportionately help minorities.”

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When Eugene Goldwasser launched the project that would become his life’s work, he thought it would only take a matter of months. Since the early 20th century, biologists had predicted that a hormone they named erythropoietin must exist to promote the production of red blood cells when the body was running low. But in 1955, nobody had found it. Working at the University of Chicago after World War II, Goldwasser was challenged by his mentor, Leon Jacobson, to find erythropoietin, or Epo as it would come to be known.

“Very few biochemists were foolhardy enough to commit themselves to working on this seemingly intractable protein,” wrote Goldwasser, who passed away last week at the age of 88. “My thought was that any reasonably good biochemist ought to be able, in a relatively short time, to purify a hormone with a measurable biological effect.”

It took 22 years. But the purification of Epo, and the hormone’s eventual commercialization as the drug Epogen, ended up being one of the most significant discoveries of its time. A godsend for people struggling with anemia, either directly or as a consequence of kidney failure, cancer, or AIDS, Epo has helped millions of patients avoid blood transfusions that were once a regular part of their disease. A less savory use of Epo, as a performance-boosting drug, led to widespread controversy in the Tour de France in the late 1990’s. The billions of dollars made off of Epogen, and the legal and political battles over that windfall, also made it an important landmark (for better and worse) in the early days of the biotechnology industry.

Goldwasser himself was the recipient of almost none of that fortune, having failed to pursue a patent on the hormone when his purification experiments finally reached fruition in 1977. For him, the pursuit of Epo was pure basic science, and the potential for clinical application, never mind the money to be made off that translation, was a low priority. In a 1996 essay for the journal Perspectives in Biology and Medicine (not online, sadly), Goldwasser wrote about how he was so unconcerned with patenting his discovery, he forgot that he had even tried until discovering an unanswered disclosure form in his files decades later.

“After submitting the form I promptly forgot about it, since nothing was ever done about filing for a patent,” Goldwasser wrote. When the hormones was eventually patented and sold by the company Amgen, Epo brought them well over a billion dollars a year in revenue.

Even in the midst of this boom, Goldwasser was more interested in the scientific history of Epo than its profitability and legal wrangling. The 1996 essay is a gripping narrative of a scientific hunt, riddled with pitfalls and obstacles that Goldwasser and his collaborators were forced to navigate in order to grab hold of the elusive Epo. The biggest obstacle was the hormone itself, which is so effective in promoting red blood cell production that it is only secreted for brief periods and in very small amounts to produce millions of cells. As Merrill Goozner, author of “The $800 Million Pill,” wrote: “the amount of Epo needed to produce that lifetime supply could be dried and formed into a tablet no larger than an aspirin.” Finding such an ephemeral factor and then gathering a quantity large enough to study and replicate it was a gargantuan task, despite Goldwasser’s early confidence.

When Goldwasser began his search, scientists weren’t even sure which organ secreted Epo. So they started with a crude experiment: removing different organs from rats and injecting them with a salt known to induce red blood cell production. When the kidneys were removed, the salt had no effect, leading the researchers to believe they had found their organ (another clue was the anemia often seen in people with chronic kidney disease).

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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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When it comes to genes, evolutionary biologists have traditionally favored seniority. Genes thought to be most essential to life must be ancient and conserved, the assumption goes, handed down from species to species as the basic instructions of life. That sharing is evident in early developmental stages, which 19th-century biologist Ernst Haeckel observed to be very similar between different organisms in his famed recapitulation theory. The genes that drive those early stages of development are also shared by creatures as different as flies, mice, and humans, lending support to the idea that the most important genes for life go a long way back on the evolutionary tree.

By comparison, new genes haven’t gotten nearly as much credit. Arising more recently in evolution’s history, rookies that only count their age in tens of millions of years were thought to be less important - providing new functions and features that were nice, but not essential. If old genes were the bread and butter of life…

“Maybe the new genes serve a function like vinegar or soy sauce,” said Manyuan Long, professor of ecology & evolution at the University of Chicago. “They make your life better, change behavior, help a male find females more efficiently, but that’s all.”

But that ageist perspective is shaken in this week’s Science, courtesy of an exciting new study from Long’s laboratory. Using the fly species Drosophila melanogaster, Long, graduate student Sidi Chen, and postdoctoral researcher Yong Zhang tested whether silencing a new gene would be as fatal as silencing an old one. With RNA-interference (RNAi), a method which interrupts the translation of genes into proteins, they silenced 195 new genes between the age of 3 and 35 million years, one at a time.

The tests found that these young, supposed “condiment” genes could be just as deadly when they were silenced. Thirty percent of the genes were fatal when knocked out, suggesting that new genes can quickly become an essential part of an organism’s survival. What’s more, new genes were nearly as likely to be essential as old genes - when RNAi experiments were repeated on a sample of older genes, a similar 35 percent of them were fatal.

“A new gene is as essential as any other gene; the importance of a gene is independent of its age,” Long said. “New genes are no longer just vinegar, they are now equally likely to be butter and bread. We were shocked.”

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The bacteria that started it all.

When scientist/entrepreneur J. Craig Venter announced that his company had created “synthetic life” in March, a predictable tsunami of media hype followed. Though the discovery was more accurately an important step in synthetic biology, rather than the creation of life from scratch in a laboratory, the story provoked rampant speculation about what this new field might be capable of. Interest in the promise and dangers of synthetic biology went up to the very top - the White House, where President Obama ordered his Presidential Commission for the Study of Bioethical Issues to look at this new science as their first item of business.

Today, seven months later, the commission’s report [pdf] is being released, with recommendations on what the federal government should do - and not do - about the growing field of synthetic biology. Our own Daniel Sulmasy, professor of medicine and ethics at the University of Chicago Medical Center and the Divinity School, is one of 13 members of the commission, and was kind enough to walk ScienceLife through the highlights of the report. The over-arching theme is one of “prudent vigilance,” Sulmasy said.

“We rejected the position that progress is so good, let’s just forget about any kind of regulation,” Sulmasy said. “But we also rejected the very cautious ‘precautionary principle,’ that says until something is proven safe we shouldn’t do it. I think that would cripple scientists and the potential of progress here that may be of significant benefit.”

Someday, synthetic organisms may provide renewable fuel sources, efficient vaccines, new ways of fighting pollution, and improved agriculture. While those applications are a long way off, Sulmasy said now was the right time for the commission to start a conversation about the ethics of such scientific breakthroughs, even if it is decades before they come to fruition. There’s a danger in being too early, he said: ethicists discussed the possibility of cloning organisms as early as the 1970’s, yet those discussions were largely unacknowledged, leaving policymakers unprepared for the ramifications of Dolly the Sheep in 1997. But open the ethical conversation too late, and it’s “like trying to put the cat back in the bag,” Sulmasy said.

“I hope that we can take a look early enough that we can have the ethical debate before the science is being done in widespread fashion and it’s impossible to regulate,” Sulmasy said.

Still, not knowing where synthetic biology may lead left the commission in a tough spot. Of the 18 recommendations listed in their report, the majority suggest using public funding organizations such as the National Institutes of Health, the Department of Energy, and NASA to share lifeguard duties over the field, without proscribing any specific restrictions. The agencies should fund promising research projects in synthetic biology, the report says, and make sure that adequate testing is done before the products of thatresearch are released beyond the laboratory.

Keeping scientists at academic institutions and private research companies in line should be possible under this structure, but the report identifies a newer, less predictable group of experimenters: DIY scientists. Shrinking costs of genome sequencing and scientific tools have led to a community of hobbyists doing synthetic biology research at home, Sulmasy said.

“There already is a lot of regulation and oversight on the academic and industrial side, so we didn’t think there was a need to create an independent commission or mechanism for assuring the safety of this work there,” Sulmasy said. “Where we did discover a gap is in a small number of people who are doing this kind of work at home and are very intrigued by it. For those who fall outside of the usual communities, we want to bring them into the fold without causing resistance.”

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(image from comics.org)

In Iron Man, Tony Stark engineers himself a robotic suit of armor that serves two purposes, fighting against the terrorists who took him captive while keeping pieces of shrapnel from puncturing his heart. Based on a new study from a University of Chicago neuroscience laboratory, wearable robots like Iron Man’s suit may also serve a dual purpose for a different type of user: quadriplegic patients.

Scientists, in an effort worthy of comic books, have successfully developed brain-machine interfaces that allow people to move computer cursors and prosthetic arms with their thoughts alone. When paralysis occurs due to a spinal cord injury or neurological disease, signals from the brain fail to reach the muscles of the body. But the brain electrical activity normally responsible for movement remains intact, and brain-machine interfaces (BMIs) seek to translate that information into the operation of an external device. One such BMI, called BrainGate, was successfully tested in quadriplegic patients 4 years ago.

However, while those patients were able to hit various computer targets and even type e-mails with their thoughts, their control of the cursor was somewhat shaky. When a person moves a computer cursor the old-fashioned way - with their hand on a mouse - information moves in two directions. Signals from the brain travel to the hand directing the movement, and sensory feedback goes back to the brain reporting on the movement’s success, both from the eyes tracking the cursor and from the location and movement of the hand in space. This latter sense, called proprioception or kinesthetic feedback, was not present in BrainGate trials; the patients’ had only visual feedback to help adjust their movement.

“In the early days when we were doing this, we didn’t even consider sensory feedback as an important component of the system,” said Nicholas Hatsopoulos, professor and chair of computational neuroscience at the University of Chicago. “We really thought it was just one-way: signals were coming from the brain, and then out to control the limb. It’s only more recently that the community has really realized that there is this loop with feedback coming back.”

To test whether adding proprioception back in would improve the performance of a BMI, Aaron Suminski and Dennis Tkach added an additional component to the BMI set-up: an exoskeletal robot arm worn like a sleeve by the subject. Monkeys trained to move a computer cursor without moving their limbs wore the robot arm, which was programmed to move in tandem with the cursor’s movement. So while the monkeys operated the cursor with only their thoughts, the arm responded to the motion and provided kinesthetic feedback to the brain.

With this additional sensory information, use of the BMI improved. As reported in the The Journal of Neuroscience, the monkeys moved their cursors to the targets faster and on a straighter line than in trials without the robot arm providing feedback. The effect could also be seen directly in the brain, where activity in the motor cortex contained more information with the robot arm than without, demonstrated by an improved signal-to-noise ratio.

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The genetic code contains only four letters. Different combinations of those letters code for an “alphabet” of 20 amino acids, which are used to construct proteins. From these small collections of building blocks, an incredibly diverse array of proteins can be constructed. But nature always craves more options, and scientists are still learning the ways it has developed to expand its biological vocabulary. With epigenetics, nature can tweak the genetic code without changing the basic four nucleotides. With protein modification, stable constructions can become dynamic machines, changing shape and switching on and off.

The laboratory of Yingming Zhao, associate professor in the Ben May Department of Cancer Research, tracks down previously undiscovered ways nature has found to customize its proteins. Usually, proteins are modified via chemistry, with molecules such as methyl groups (methylation) or phosphate groups (phosphorylation) added to the side chains of amino acids. Attaching these groups can dramatically change the shape and function of a protein, increasing its activity, decreasing it, or sending it to the cellular trash dump. On a larger scale, errors in these modifications can have dramatic consequences; for example, excessive phosphorylation has been targeted as a cause of many cancers, and modification may play a role in aging.

“Think of comparing someone who’s really young, say 1 month old, to someone who is 90 years old,” Zhao said. “Their cells and tissues function so differently. In my personal view, a major pathway that causes those differences is protein modification.”

In the last three years, Zhao’s team has added two new modifications, lysine propionylation and lysine butyrylation, to the menu of protein modifications. But this week, his lab publishes findings in Nature Chemical Biology on a third modification that may be even more biologically important: lysine succinylation. The addition of a succinyl group to the amino acid lysine is a big change in chemical terms, changing the electrical charge of lysine from positive to negative.

“If you take away the positive charge by acetylation, it becomes more hydrophobic, so in terms of its property it is dramatically changed,” Zhao said. “When you put succinylation, it goes from positive charge to negative charge, it’s a two-charge change. The chemical importance of the change with lysine succinylation is more than lysine acetylation and methylation, two protein modifications with critical cellular functions.”

The discovery of lysine succinylation started with a mysterious, very tiny shift in weight in the protein isocitrate dehydrogenase, a member of the citric acid cycle you may have memorized in high school. By the size of the shift (100 Daltons, or one hundred octillionth of a gram) the likely candidate was succinyl, and a series of experiments conducted by a research team led by Zhihon Zhang and Minjia Tan confirmed the hypothesis. By developing an antibody for succinylated lysine, the researchers then confirmed that this modification was common in nature - appearing in everything from e. coli bacteria to cancer cell lines from humans. That persistence is part of the argument that lysine succinylation is an important function, Zhao said.

“It’s evolutionarily conserved and present in all types of cells we examined, from bacteria to mammalian cells,” Zhao said. “It is also very abundant: it’s not only present in a few proteins. Finally, it is a very dynamic protein modification that responds to diverse cellular environments.”

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Artist's rendering of the new Eckhardt Center (Courtesy of HOK/JCDA/AJSNY)

Today, the University of Chicago announced plans to construct the William Eckhardt Research Center, an innovative new building along Ellis Avenue that will be home to many researchers in the physical sciences.

But just as newsworthy as the new building is one of its prominent tenants: the Institute for Molecular Engineering, the largest new department launched at the University since the Harris School of Public Policy in 1988. The Institute, called the IME for short, will serve as a bridge between the Physical Sciences Division and the Biological Sciences Division for shared goals in research and education.

But what exactly is molecular engineering? The specific mission of the IME will be set next year when a director is named, but the general direction of this exciting new discipline was summarized last year by a faculty committee appointed to evaluate the IME’s creation. ScienceLife talked to a few of those committee members to learn about what molecular engineering is, what kinds of problems it might solve, and what kind of students it will create.

Biology and medicine is increasingly focused on how small scale interactions are important for both normal function and disease. Simultaneously, engineers grounded in physics and chemistry are looking toward biological systems for ideas and solutions. Increasingly, physical and biological sciences are speaking the same language, said Raphael Lee, Paul and Ailene Russell Professor of Surgery, Medicine, and Organismal Biology & Anatomy.

“On the molecular scale, behavior is described by laws of physics and chemistry,” Lee said “The rules of biology and physics are identical at the molecule scale. That’s where the fields boundaries blur and overlap.”

At this common ground, molecular engineering provides a skill set for the next generation of scientists to address the world’s biggest problems. The knowledge gathered through basic science in biology, chemistry, and physics laboratories can be combined and applied to major issues, such as providing clean water to undeveloped countries, or developing more efficient energy sources.

“This is making the science much more applied: we know how it works, so let’s try to make it better. How do we apply that knowledge to these problems that we see,” said Erin Adams, Assistant Professor of Biochemistry and Molecular Biophysics.

Molecular engineering innovation may also lead to the development of new technologies for medical care. Scaffolds for stem cell treatment might be designed through engineering, chemistry, and biology collaboration. Animals that have evolved natural self-healing abilities could inform the design of materials that repair themselves, which could in turn be used for the design of industrial products and medical devices.

“I think it’s entirely possible that new kinds of tools could be generated in molecular engineering that would have therapeutic implications,” said Julian Solway, Professor of Medicine and Pediatrics. “The problems that we’re addressing are the same problems, and the solutions that we want to find are well-suited to be approached by both camps.”

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Imagine There’s No Hunger

This post is going up around lunchtime, and you might be just now picturing what you’re going to eat. There are those healthy whole-wheat pasta leftovers in the fridge, but just down the street is a deli where you can purchase a giant Italian sub with hot peppers and cheese and a bag of chips on the side. Just the thought of that delicious sandwich is making your mouth salivate and your stomach grumble in anticipation. Wait, were we talking about you, or me?

The ability of people to make themselves hungry just by imagining food has always baffled psychologists, who would predict just the opposite response. Using imagination for habituation, the gradual diminishing of a stimuli’s power to provoke a response with repetition, is a classic tool of psychological treatment. For example, people with phobias are often instructed to repeatedly imagine the cause of their fear (spiders, heights, airplanes) until their emotional response subsides. By that theory, repeatedly imagining a delicious pizza should eventually make you less hungry for a slice, rather than increase craving.

But maybe people are just imagining the wrong thing, thought researchers from the business school at Carnegie-Mellon in this week’s Science. Instead of imagining the food before it is eaten, perhaps people could imagine actually eating that food to habituate themselves against its wily charms. Using a particularly seductive denizen of the office vending machine, M&M’s, the authors instructed their subjects to imagine eating 30 pieces of the candy in succession, like picturing the process of inserting 30 quarters into a vending machine. This tedious fantasy actually worked when the subjects were subsequently given a nice big bowl of M&Ms - subjects who imagined eating 30 pieces of candy ate less than subjects who only imagined a 3-piece snack, or no snack at all. The trick was found to be stimulus-specific, in that a session of imaginary M&M eating had no effect on subsequent eating of another snack; in this case, cheese cubes.

Aside from it’s dietary implications, the study is a pretty amazing demonstration of the power of imagination - “The difference between actual experience and mental representations of experience may be smaller than previously assumed,” the authors write. But it’s unlikely that anyone will incorporate this imagination trick into a get-thin quick diet plan, as you can’t sell a customer the ability to imagine eating unhealthy food, and therefore can’t hire Kirstie Alley to endorse it. But it is something we can all try for free, at home or at our office desk. So while I write the rest of this post, I’ll devote part of my mind to imagining the laborious consumption of that delicious Italian sub sandwich, rather than the sandwich in all it’s pre-eaten glory.

[H/T to the Wall Street Journal Health Blog for the article.]

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Life found on...California (photo from NASA)

By now, you’ve probably heard about the “alien” arsenic bacteria discovered in a California lake…and if you’ve been following the story closely, you might have a neck ache from all the twists and turns. When word of a NASA press conference on “astrobiology” broke last week, many hoped that the first evidence of extraterrestrial life was about to be released. But then the news turned out to be the discovery of a bacteria that can grow using the poisonous element arsenic, not little green men. But wait - the substitution of arsenic for phosphate (one of the key six ingredients for life) at least meant that the rules for life had been rewritten, still a cool finding. But wait again!

Over the weekend, scientists began lining up to take chunks out of the Science paper containing the findings from NASA and US Geological Survey scientists. First, microbiologist Rosie Redfield dissected the methodology of the paper and found it considerably lacking, if not intentionally deceptive. Science writer Carl Zimmer followed with damning comments from several scientists supporting Redfield’s take and adding more fuel to the fire…even going so far as to say that the paper should not have been accepted by a journal and published. And even more writers piled on with critiques of how NASA and Science promoted the research, and how media outlets handled the science. It’s all very confusing.

One interested observer is Jack Gilbert, assistant professor of ecology & evolution at the University of Chicago and an environmental microbiologist at Argonne National Laboratory. Gilbert uses genetic and computational techniques to study microbial function and diversity in their natural environments, a field where an arsenic-based bacterial species would be big-time news. But Gilbert finds the paper far less momentous than some of the original, breathless coverage.

“This is just another example of a microbe that has found a niche that enables it to survive in areas where other microbes would not be able to survive,” Gilbert said in a phone interview yesterday. “Bacteria are incredibly versatile, that’s all this paper is really saying.”

A resistance to the poisonous effects of arsenic would be helpful for the bacteria, called GFAJ-1 (pictured at right), to survive in its natural habitat of Mono Lake, where arsenic levels are extremely high. But the experiments published in Science don’t look at GFAJ-1 in its natural environment, but rather in the laboratory, where researchers artificially removed the element phosphate (used in building DNA and many important proteins) and replaced it with increasing levels of arsenic. The big finding was that this inhospitable environment did not kill the bacteria - and at some arsenic concentrations, it could actually grow and reproduce, purportedly by building DNA and proteins with arsenic instead of phosphate.

One of Redfield’s main objections is that the treatments used in these experiments probably didn’t remove all of the phosphate, and trace amounts left behind could have allowed the bacteria to survive with no novel biological tricks. Gilbert said he hadn’t yet read Redfield’s post, but agreed that he would have requested the authors run more experiments and controls to shore up their conclusions. But now that the paper has been published, he agrees with the authors when they say that the proper forum for criticism is through the peer-reviewed journals.

“As an impatient person, I find peer review incredibly frustrating, but it’s there for a very good reason,” Gilbert said. “Peer review enables us to question the findings in other research articles, and that’s essential if we want to figure out if the piece of work isn’t up to scratch.”

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In its sedative normalcy, the Chicago suburban sprawl would seem an unlikely setting for the noble quest of solving the basic laws of nature. But just up Farnsworth Avenue from the outlet mall and the minor league ballpark lies the 6,800-acre campus of Fermilab National Accelerator Laboratory, where scientists have spent the last 40 years simulating the birth of our universe to better understand the laws of matter and energy. What looks like just another stretch of undeveloped land waiting to be paved over and turned into a strip mall actually hides the Tevatron particle accelerator, a 4-mile long ring that can bring protons and antiprotons almost to the speed of light before slamming them into each other, revealing the smallest building blocks of the universe.

It’s pretty intoxicating stuff, and even the scientist who has overseen most of Fermilab’s rich scientific history remains excited about it. At age 88, Leon Lederman, director emeritus of the laboratory (and a professor emeritus at UChicago), didn’t sound like his enthusiasm for high-energy particle physics has diminished as he spoke to the University of Chicago Medical Center Radiology department on Monday. The official mission of Fermilab is to “advance the understanding of the fundamental nature of matter and energy by providing leadership and resources for qualified researchers to conduct basic research at the frontiers of high energy physics and related disciplines.” But Lederman’s short version was even better: “at Fermilab, we concentrate on how the world works.”

Though Lederman’s talk was called “Imaging the ‘God Particle’” - referencing his 1993 book on the hunt for the Higgs Boson, the missing piece of the Standard Model of Physics - he stuck to mainly to Fermilab basics. Sitting within the crowd and switching out faded transparencies on an overhead projector, Lederman’s talk had an old-school feel, but it fit the timelessness of the research. Rather than a data presentation, it was something like a slideshow recap of a vacation - “How I Spent My Summer at Fermilab.” Lederman laced his talk with the dry humor on display in his book (a recommended read for anyone looking for a quick education in particle physics), and with simple explanations of a very complicated field.

“There are head-on collisions, particles come off, they are detected, recorded, and in this way we learn something about the forces that moderate the behavior of these particles,” said Lederman, the winner of the 1988 Nobel Prize in Physics.

The vintage look of Lederman’s photos belied the fact that important work is still underway at Fermilab, despite the opening last year of the Large Hadron Collider at CERN in Geneva, Switzerland. Particles still fly around the Tevatron ring seven days a week (as you can learn on the accelerator’s twitter feed), and scientists believe there are still important things to learn even though the LHC is now  top dog in the high-energy physics race.

“We collaborate and we also compete” said Lederman of the CERN-Fermilab relationship. “It’s a nice friendly competition, in which we secretly try to get more data than they do.”

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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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Even before the very rules of life were changed by the discovery of an arsenic-based microbe in a California lake (or were they? More next week.), this week seemed to be full of strange and interesting science involving animals. While ScienceLife works on a bunch of research that is under embargo until later this month (disclaimer: none of them involve extraterrestrial life), here are a few bullet-pointed studies that inspired awe and wonder this week.

• Optogenetics is the technique of creating mutant mice with cells that can be modulated with flashes of light, which is awesome. For example, a scientist can introduce a gene into a mouse strain that makes motor neurons sensitive to light, and when light is shined at those neurons, the mouse starts running. Now, researchers from Stanford and UT Southwestern have used optogenetics in the frontal cortex of a mouse strain, and found a way to produce anti-depressant-like effects (pdf). As covered by David Dobbs at Wired, the technique may offer a new non-invasive way of treating depression way down the line; for now, optogenetics requires a brain implant, which is less than ideal clinically.

• Telomeres, the long repeated sequences at the end of chromosomes, were a fashionable scientific buzzword before optogenetics was even a glimmer in science’s eye. With their companion enzyme telomerase, telomeres were hyped to be the genetic key to the  “fountain of youth,” the biological source of the cell damage that accompanies aging. But despite being the subject of last year’s Nobel Prize in Physiology or Medicine, the excitement about telomeres seemed to have faded out. But an exciting new study published in Nature this week may reignite that flame, as scientists at Harvard reversed the premature aging of a special mutant mouse with telomerase treatment. Wired, Ars Technica, and the Wall Street Journal discussed this “Ponce de Leon” effect, but Discover blog 80beats urges patience for those waiting on anti-aging pills.

• Scientists have long used animal models to study the neurobiology of fear in laboratory settings. But how do you realistically recreate situations that would cause a rat to be scared in the wild in the predator-free world of the animal facility? For one group of scientists, the answer was Robogator, a simulated predator designed to leap out at rats as they moved foraged for food in their lab environment (you can download video clips here). Researchers looked at how close the rat would approach Robogator before and after a lesion of the amgydala, a brain region thought to be involved in fear response. Before the lesion, the rats would only get food 10 inches or less from the entrance to their chamber, but after the lesion, they would go as far as 50 inches, sometimes even approaching and investigating the robot (video) without fear.

• Here’s a novel effect of environmental pollution upon wildlife: when ibis birds of South Florida are exposed to the most potent form of mercury, they opt for homosexual pairings over heterosexual matches.

In a time of worrying American health statistics, some states definitely have it worse than others. On many measures of health and health system performance, Oklahoma ranks near the bottom of the list - or in the case of fattest states, near the top. At his talk for the MacLean Center Seminar Series last month, Gerard Clancy illustrated his state’s health woes with a collection of photographs from the Oklahoma State Fair, including the “donut burger” and the elegantly direct deep fried butter.

As Dean of the College of Medicine at the University of Oklahoma-Tulsa, Clancy’s immense challenge is to find new ways of improving health in this decidedly unhealthy setting. To do so, Clancy has overseen a dramatic change in the medical school’s curriculum, mission, and even name, rechristening the program as the OU School of Community Medicine. Clancy and colleagues redirected the school to focus on health care access and training medical students in primary care and community health, all in the context of national health care reforms and their new emphasis on reimbursing quality over volume.

“Our belief is that we’re going to have to modify how we deliver health care to have a model teaching environment for our medical students,” Clancy said. “We don’t want to have a teaching model that is archaic compared to where health care is going to be soon. So we are rapidly changing how we deliver health care.”

That plan revolves around new community efforts, particularly in the poorer neighborhoods of North Tulsa, where life expectancy lags 14 years behind the more affluent south half of the city. Deploying the “Starbucks model,” Clancy said the school is trying to build health care access points on every corner, with more than 300 doctors working at over 50 sites. As a hub, the school broke ground on the Wayman Tisdale Specialty Health Center, named for the college basketball great who died of osteosarcoma in 2009.

But in the week before the groundbreaking ceremony, Clancy said the school learned a valuable lesson about not forgetting the “community” in community health. A newspaper ran a front-page editorial headlined “Is Tulsa North Being Pimped by OU?,” which challenged why the university was only providing health care without addressing social determinants that create poor health: lack of education, jobs, and other services.

“This was a big lesson for us to learn,” Clancy said. “When we met with the legislators, and the leaders of North Tulsa, and the writers of the article, the key line was ‘You don’t get it. We want you to bring the full resources of the University of Oklahoma to us, not just the clinics.’”

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