In biology, fitness can be crudely measured by a simple method: counting. If a particular species is well represented in a particular ecosystem, one can conclude that evolution has treated them well, with circumstances allowing them to thrive. It’s a bit simplistic to declare evolutionary winners or losers, but a species that over-populates an island is certainly doing better than the another species that goes extinct.

The same logic can be applied to individual genes - if a particular gene is seen in many different species and environments, one can reason that it’s doing something right relative to genes that have fallen off the map. That was the approach taken by Ramy Aziz of the University of Chicago Computation Institute and collaborators in an unusual paper published earlier this year. Aziz and fellow researchers used the thousands of complete genomes now available to scientists and the new concept of “metagenomes” to take a kind of gene census. Their hunt produced a unique class of genes that is both more abundant and ubiquitous in nature than any other: the transposases.

Transposases are enzymes with a strange role. Like editors, their main job is cutting and pasting, though instead of working with text or video, transposases rearrange DNA. Their existence was first detected by the famed plant geneticist Barbara McClintock, who won the Nobel Prize for characterizing the “jumping genes” moved around by transposases in maize. This reshuffling of the genome can sometimes be harmful to a species, but it also creates increased diversity that can be evolutionarily advantageous, as diverse populations are more resistant to shifting environmental pressures.

Aziz and his colleagues didn’t go looking for tranposases when they organized their gene census. Their study sought to find the most abundant (how often it appears) and ubiquitous (how many species in which it appears) genes in nature, and they used 2,137 genomes from bacteria, viruses, animals, and plants for the search. Combining all those genomes and analyzing them with the computers at Argonne National Laboratory turned up a lot of transposases - 26,625 to be exact, almost 1 percent of all protein-encoding genes. On average, a genome contains more than 38 different transposases.

Simply pooling all the known complete genomes created a bias, as most of the bacteria and viruses that have been sequenced are those most relevant to humans for agricultural or medical reasons. So the team also used metagenomics, a broad sample of the genetic diversity present in a particular ecosystem such as ocean, soil, or even the human gut. In this data set, the transposases again were the most commonly found genes, and appeared in almost every ecosystem sampled, making them kings of the global genome.

“We demonstrate that these jumping genes are almost omnipresent in every ecosystem that contains nucleic acid-based life forms,” the authors write.

But why are transposases so successful in the arena of genetic competition? The authors point out that they are prime examples of “selfish genes,” as coined by Richard Dawkins, Francis Crick, and others. One can even think of transposases as particularly accomplished parasites inhabiting the genomes of everything from bacteria to humans, surviving by moving and replicating themselves at will. Yet for the organism they are parasites-with-benefits, with the ability to “induce advantageous rearrangements or enrich the host’s gene pool,” the authors write. Rather than being creeped out by these genomic invaders, perhaps they are deserving of a thank-you card.

“They may offer a selective advantage to the genomes and ecosystems that they ‘parasitize,’” the article concludes. “The diversification they induce in these genomes and ecosystems is arguably an essential way of maintaining, diversifying and evolving life on our planet.”

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Aziz RK, Breitbart M, & Edwards RA (2010). Transposases are the most abundant, most ubiquitous genes in nature. Nucleic acids research, 38 (13), 4207-17 PMID: 20215432

A diagnosis of diabetes brings with it a plethora of lifestyle changes. Patients must switch up their diet and exercise habits, take on a new routine of daily medications and injections, and keep an eye on their blood sugar. But another potential change under the cloud of diabetes is even more personal: the diabetic’s sex life. With diabetes rates on the rise, and the lifespan of those with diabetes gradually lengthening, it would be informative for doctors to know how often their older, diabetic patients are having intimate moments and whether the disease impacts their sexual health.

In an article published last week in the journal Diabetes Care, a team led by Stacy Tessler Lindau at the University of Chicago Medical Center shed light on the previously hidden sex lives of elderly diabetics. With a dataset of interviews with older adults - in fact, the same dataset used for the medication disparities study ScienceLife wrote about last week - the researchers were able to analyze the sexual health and un-health of people with diagnosed and undiagnosed diabetes. The results found that diabetes doesn’t take as big a bite out of a person’s sex life as might be expected - though all is not entirely well.

“Patients and doctors need to know that most middle age and older adults with partners are still sexually active despite their diabetes,” said Lindau, an associate professor of obstetrics and gynecology. “However, many people with diabetes have sexual problems that are not being addressed.”

When it comes to elderly diabetics who are married or living with a partner, the numbers on who remains sexually active are in line with the general population. Broken down by gender, the same sexual gap appears with diabetics as well - diabetic men between the age 0f 57 and 85 are more than twice as likely to be sexually active as diabetic women of the same age. A similar imbalance was seen for the discussion of sexual issues with a physician: 46.8 percent of men said they had talked with a doctor about the topic, compared to only 18.8 percent of women.

“Failure to recognize and address sexual issues among middle-age and older adults with diabetes may impair quality of life and adaptation to the disease,” said Marshall Chin, senior author of the study and professor of medicine. “Sexual problems are common in patients with diabetes, and many patients are not discussing these issues with their physicians.”

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

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

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

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

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The story of bisphenol A (BPA), the organic compound used to make the stiff plastic of water bottles, CDs and other consumer products, has been well told by the media. Once thought to be harmless to humans in the amounts used for plastic production, BPA has since been deemed an “endocrine disruptor” by researchers finding disturbing results in rats and humans. While debate continues to rage over how dangerous the compound really is, the battle is increasingly split into the familiar teams of physicians/scientists/consumer groups vs. industrial lobbyists. But how did BPA become the latest toxic substance to make the leap from journal articles to newspapers?

BPA’s narrative arc and current recommendations for avoiding it were the topics last week at the Department of Pediatrics weekly Grand Rounds. Susan Buchanan and Mark Mycyk of the Great Lakes Region Pediatric Environmental Health Specialty Unit visited to give a tag-team presentation on how the alarm was sounded on BPA and how the regulation controversy has unfolded around the world.

As Mycyk framed it, the discovery of BPA’s harmful effects resulted from nothing less than a revolution in toxicology, the study of what is or isn’t a poison. The answer isn’t always clear, Mycyk said, quoting 16th century scientist Paracelsus: “All things are poison and nothing is without poison, only the dose permits something not to be poisonous.” How scientists calculate what that dose is for each compound has changed over the years, but still relies on testing high doses in animals (usually rats) and deploying math to extrapolate to low doses and humans.

That’s easy to do when the dose-response curve is a straight line - trace backwards from the point where the compound is toxic to where it is presumably safe, and voila. This method was traditionally used for chemicals encountered daily in the form of pharmaceuticals, pesticides, and plastics, Mycyk said.

“Big doses cause big problems, but they are incorporated into everyday life at lower doses which were initially considered safe doses,” Mycyk said.

But as scientific methods and instrumentation improved, the ability to test lower doses revealed some disturbing trends. For some chemicals, the dose-response curve was a not a straight, upward line, but an upside-down U-shape - a “non-monotonic dose-response curve.” For such compounds, the toxicity can actually be higher at low or intermediate doses, or the effect can change from stimulation to inhibition, throwing off all scientific estimates.

BPA made for a striking and disturbing example of this toxicological revision. The compound was known since the 19th century as a “weak estrogen,” chemically similar to the hormone but thought to be biologically inert in anything but massive doses. But in the last 10 years, new studies have revised the acceptable daily intake for human beings downward by as much as 100 times. Animal studies have found that very low BPA levels produce higher rates of mammary tumors, decreased sperm, and early puberty. A human study that looked at BPA concentrations in urine found that high levels of the chemical correlated with increased rates of cardiovascular and liver disease.

“This is very, early preliminary literature,” Mycyk said. “But this is a really important study that generated a lot of media attention and a lot of attention from science and industry. It’s very scary; it’s actually changed our understanding of how these endocrine disrupters work.”

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When President Obama signed an executive order last March loosening the restrictions on embryonic stem cell research, it seemed like the shackles were finally off for good. The new policy rolled back the “Bush compromise” forbidding federal funding of research on any newly created stem cell lines, leaving only 21 lines (at most) eligible for the grants that support the vast majority of laboratory research in the United States. After Obama’s decision, the floodgates didn’t exactly open, but embryonic stem cell research received a significant boost, with more than 300 projects receiving nearly $150 million in National Institutes of Health funding. In the 18 months since the executive order was signed, the number of eligible stem cell lines has expanded from 21 to 75.

But just as American stem cell research was starting to enjoy the regained momentum, an emergency brake was pulled this week by a federal judge in the District of Columbia. Judge Royce Lamberth issued a temporary injunction Monday that found Obama’s executive order in violation of the “Dickey-Wicker amendment,” a ban on giving federal money to research involving the destruction of human embryos that has been attached by Congress to each year’s federal spending bill since 1996. Lamberth interpreted research conducted on embryonic stem cell lines, even long after the original destruction of an embryo to create those lines, as being illegal under the amendment. Despite previous rulings that differentiated between research on an embryo and research using stem cells derived from an embryo, Lambeth ruled that (at least temporarily) NIH funding of embryonic stem cell (ESC) research must stop.

“ESC research is clearly research in which an embryo is destroyed,” Lamberth wrote in the injunction. “To conduct ESC research, ESCs must be derived from an embryo. The process of deriving ESCs from an embryo results in the destruction of the embryo. Thus, ESC research necessarily depends upon the destruction of a human embryo.”

The reaction from the scientific community, as you might guess, has been less than celebratory.

“This decision has the potential to do serious damage to one of the most promising areas of biomedical research, just at the time when we were really gaining momentum,” said Dr. Francis S. Collins, director of the National Institutes of Health. The ruling, he added, “just pours sand into that engine of discovery.” (New York Times, 8/25)

“‘I have had to tell everyone in my lab that when they feed their cells tomorrow morning, they better use media that has not been funded by the federal government,’ said Dr. George Q. Daley, director of the stem cell transplantation program at Children’s Hospital Boston, referring to food given cells. ‘This ruling means an immediate disruption of dozens of labs doing this work since the Obama Administration made its order.” (New York Times, 8/24)

“Basically, they are saying that all ESC research is a part of a broader system of research that includes the initial destruction of embryos. Which would be kind of like saying that all research into nuclear power stems from the Manhattan Project,” he says. (Hank Greely, director of the Center for Law and the Biosciences at Stanford University, Nature News, 8/24)

The ruling hit close to home too, as our own John Cunningham, professor of pediatric and director of hematopoietic stem cell transplantation, told Chicago Public Radio yesterday. Cunningham, who hopes to use embryonic stem cells to study leukemia and other blood diseases, expressed his frustration at having to once again put all such projects on hold due to politics and legal rulings.

“As we go through this process of stopping and going and stopping and going, it really retards our ability to make decisions based on science,” Cunningham told WBEZ.

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When the FDA adds a “Boxed Warning” to a drug - known casually and more dramatically as a “black box” - it can have dramatic consequences. The information is intended to warn physicians of potential adverse effects associated with the drug, issues that are not deemed serious enough to pull the drug from the market but which should prompt extra attention and care. Antidepressants, the diabetes drug Avandia, and Depo-Provera birth control have all received black boxes in recent years, prompting widespread media coverage and medical comment.

Earlier this year, the anticoagulant medication clopidogrel (marketed as Plavix) became the latest drug to be black-boxed by the FDA. The warning fit the purported age of genetic medicine, as it was meant to draw attention to certain patients for whom the anti-clotting drug is less effective due to the presence of a gene variant for an important enzyme. These “poor metabolizers” exhibited reduced ability to convert the drug into its active components, and the black box warned that physicians should run genetic tests and consider alternative treatments in patients with the polymorphism.

But clopidogrel has become an important medical tool, used in millions of patients at high risk for heart attack, stroke, and other cardiovascular events. The drug has increasingly been incorporated into the long-term care of patients with drug-eluting stents - devices implanted to keep arteries open that secrete medication to prevent the vessels from re-narrowing. In patients where genetics renders clopidogrel less effective, the lost protection can lead to a stent thrombosis (where a clot forms on the device and blocks the artery) or other grave problems. Those concerns, and the expense of conducting genetic tests in every patient, have sent ripples through the field of interventional cardiology, said Sandeep Nathan, assistant professor of medicine at the University of Chicago Medical Center.

“There’s a growing recognition that this sort of formulaic approach to anti-platelet therapy is probably not a good idea,” Nathan said. “What has been brewing as a suspicion for well over a decade has come to an explosive head in the past one or two years.”

In response, Nathan has launched a two-pronged research and clinical effort to rethink current use of clopidogrel while seeking the best possible way to address risk in the future. Instead of waiting for a post-stent adverse event to tragically prove a patient’s insensitivity to clopidogrel, Nathan’s group has become one of the first to offer anti-platelet testing before the stent is implanted in patients at high-risk for the drug being ineffective.

“I view this as testing a parachute. You better be sure that the pack you just strapped on before you jumped out of a plane actually contains a parachute and not camping gear,” Nathan said. “If somebody implanted a drug-eluting stent in me, you better believe that I’m going to want to know if the drug that is my sole protection against a catastrophic, potentially life-ending event, is working.”

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A great deal of attention has been paid in recent years to the issue of racial and ethnic health disparities. Statistic after statistic reveals that minorities in the United States, particularly African-American and Hispanic populations, are in poorer health on average compared to American whites. Infant mortality, heart disease, diabetes, obesity, cancer and other maladies appear in often shockingly higher rates in minority populations, reflecting differences frequently attributed to socioeconomic factors and access to quality health care. But a new study by University of Chicago Medical Center researchers finds that a major contributor to those disparities might be traced back to what’s in the medicine cabinet.

The National Social Life, Health, and Aging Project (NSHAP) is a research effort launched out of the University of Chicago to study a large sample of older Americans. In 2005 and 2006, more than 3,000 in-home interviews were conducted across the country with people between the ages of 57 and 85 about their social activity, their health, and their medical care. As part of the interview, researchers not only asked the subject what medications they were currently taking, they looked at the drugs with their own eyes, taking a medication inventory “by direct observation.”

That thorough scan allowed Dima Qato, Caleb Alexander, and colleagues to analyze racial and ethnic patterns of medication use with unprecedented high fidelity. Previous studies which used insurance claims or prescriptions written to measure medication usage missed a key human factor, said Alexander, assistant professor of medicine.

“As we all know from own experience, what you are prescribed and what you take are often quite different,” Alexander said. “This data was unique in that it allowed for us to observe, from a nationally representative sample of individuals, the medicines people were actually taking.”

The analysis focused on medications prescribed to people at high risk for cardiovascular disease, a condition that has seen great progress recently in preventive medicine. Those included both the cholesterol-lowering prescription drug class of statins and the well-known over-the-counter drug aspirin, which is recommended to people at risk of heart attack and stroke for its anti-clotting abilities. Before the researchers even got to comparing different races and ethnicities, a disturbing overall trend appeared regarding use of these medicines.

“We found that across the board, regardless of race, there was evidence of under-use of both stains and aspirin,” said Qato, a research associate in the Department of Obstetrics & Gynecology.

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The link between sports-related concussions and severe brain injury has been percolating in the press for several years now, due mostly to the tireless reporting of Alan Schwarz at the New York Times. But until this week, the research was lacking a prominent face, with most of those found to have suffered from early dementia and even death after multiple concussions unknown to all but the biggest football fans. That changed Wednesday with an article by Schwarz with an impossible to ignore hook: what if Lou Gehrig didn’t have Lou Gehrig’s Disease? In the ensuing days, the story has gained traction around the world, but also generated some justifiable skepticism.

That speculation (based on particularly circumstantial evidence) was an extension of an article published this week by researchers with the Center for Study of Traumatic Encephalopathy, which has led the way on the link between concussion and brain disorders in athletes. Previously, the group had found that deceased football players who had suffered multiple concussions during their careers, such as Lou Creekmur and Mike Borich, had several physical markers of Alzheimer’s disease despite dying at a young age. The new study shifts the focus to ALS, or amyotrophic lateral sclerosis, which was diagnosed in Lou Gehrig, prompting one of the most famous speeches in sports history.

In three athletes diagnosed with chronic tramuatic encephalopathy (CTE), the Alzheimer’s-like condition reported earlier, the researchers also found symptoms that resembled ALS: muscle weakness, atrophy, and spasticity. Autopsies on the athletes also found extensive death of motor neurons - the cause of ALS - but test showed that the damage resembled the brain damage seen in CTE rather than typical ALS damage. That suggests that brain traumas suffered during athletic competition can produce damage that simulates not one, but two of the most frightening neurological disorders. With exquisite timing, Carl Zimmer had a story at Discover the same day on just how such traumas could irreversibly damage neurons by stretching and contorting their string-like axons.

But while the science is interesting (and frightening), the link to Gehrig is shakier. Though the baseball player does not appear in the scientific article, the authors use Gehrig as a prominent example in the New York Times article, and cite newspaper records of the famous Ironman suffering head injuries in games but returning to play again the next day. But since his remains were cremated and his medical records remain confidential, there’s no way to tell whether Gehrig truly had ALS or the CTE-related faux-ALS described in the new article. That’s one of many criticisms Gary Schwitzer raises in his critique of the NYT article, alongside a neurologist urging caution regarding a journal publication based on a mere three case studies.

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One typically thinks of a high school science project as something involving frog dissection or baking soda and volcanoes. Less often do you see high school students presenting posters on communication between medical residents and patients who leave the hospital against medical advice. But the Training Early Achievers for Careers in Health Program, or TEACH, prepares students for a future in medicine and research with the real, undiluted deal, a summer studying an important aspect of hospital operations.

Since 2004, more than 70 students from the University of Chicago Collegiate Scholars Program have willingly traded a significant portion of their summer break to assist on a TEACH project. Groups of high school students are connected with an UChicago undergraduate, a student from the Pritzker School of Medicine, and a faculty advisor to tackle a research topic. At the end of the summer, those research projects are presented by the high schoolers in a poster session attended by physicians and social scientists.

This year’s session, held in early August, grouped the students into four research “teams”: Team Sleep, Team ESM Pain, Team AMA, and Team Handoffs. But this was no summer camp three-legged race; their posters covered topics that appear frequently in the highest-profile medical journals and conferences.

Tenika Walker, working with undergraduate student Arshiya Fazal, presented on the effects of hospital sleep - or lack thereof - on the blood pressure of inpatients. With the noisy overnight environment of the hospital ward and occasional late-night and early-morning tests, patients in the hospital slept an average of 2 hours less each night compared to at home. The sleep loss led to more than just baggy eyes, as the study found that 10 percent less sleep raised blood pressure by an average of roughly 3 mm/Hg.

“The hospital is supposed to be a place of healing, but unfortunately sometimes it’s not,” Walker said. “In the future, we hope to inspire hospitals to consider patient’s sleep.”

Where patients may benefit from fewer interruptions during the night, another poster focused on the frequency of contact with physicians, nurses, and other staff members during the daytime. To do so, they used an “experience sampling method,” a method of measuring a patient’s experience in the hospital. Throughout the day, researchers William Bernstein, Zikra Mohideen, Andres Nicodemus, and Ethalle Thompson would stop by patients’ rooms and ask who was with them. They found that the most frequent visitors were family members, with nurses close behind and physicians a rare sighting (though the students suggested the timing of their sample may have missed early-morning doctor rounds).

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Since the middle of the 20th century, fighting air pollution has been a primary goal of the growing environmental movement in the United States and around the world. Encounters with smog and toxic gases inspired waves of public anger and protest that led to Clean Air Acts being passed in several countries and a steady progression toward tighter standards. But most of these efforts have concentrated on pollutants in the air outside the home produced by factories, automobiles, and other industrial sources. Meanwhile, another source of air pollution closer to home has gone unnoticed, even as it causes potentially millions of death in the developing world.

The main cause of indoor air pollution, explains Sola Olopade, professor of medicine at the University of Chicago Medical Center, is the burning of biomass for cooking food. In impoverished areas without access to electricity, people resort to using firewood, agricultural residue, and even cow dung as fuel for their kitchen stoves. In structures with poor ventilation, the burning of these items can create a high concentration of toxic fumes with serious health effects for those exposed.

“The problem is when you use firewood to cook, the smoke from it contains a lot of polluted dust that is carcinogenic and can also lead to airway damage and infection,” said Olopade, who is also clinical director of the University of Chicago Global Health Initiative. “When you look at it globally, there are about 3 billion people, mostly women and children, who are exposed to indoor pollution from using firewood to cook.”

The World Health Organization estimates that indoor air pollution is responsible for roughly 1.6 million deaths each year, from acute lower respiratory infections, chronic obstructive pulmonary disease, lung cancer, and other diseases. Half of those deaths are children, and nearly a third are children under the age of five, Olopade said.

“To put it in the right context, indoor pollution from biomass contributes to about 2.6 percent of the global burden of disease, actually kills more people every year than HIV and maybe even malaria, and yet nobody knows about it,” Olopade said. “So if we can accomplish bringing sensitivity or attention to this problem, and use it to influence policy and help people who are poor and would otherwise have no opportunity to have more efficient stoves, I think we will be very delighted.”

Just such an effort is currently underway thanks to a grant awarded to Olopade by the CHEST Foundation, an organization of American pulmonologists. Olopade has traveled back to his birth country of Nigeria to launch an effort against indoor air pollution in three rural communities named Eruwa, Igo-Ora, and Abanla. While doing a previous study on asthma in Nigeria, Olopade said he found that an overwhelming number of asthmatic children experienced high concentrations of toxic fumes at home.

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The Darwin/Chicago conference in Ida Noyes, October 2009

I’ve recently stumbled across two veritable smorgasbords of video content from events covered right here on ScienceLife. The first, the Darwin/Chicago conference that took place last October, had already yielded some video lecture bounty, but I’m pleased to report that the rest of the conference (with the exception of the opening night’s session) has been posted on the official website. I highly recommend:

Peter & Rosemary Grant - Whose accents are as delightful as their Galapagos Islands research, made famous by Jonathan Weiner’s The Beak of the Finch.

Eric Lander - The first author on the Nature paper that published the human genome and now a prominent scientific advisor to President Obama, Lander bridged Darwin and early genetics with our modern genomic era, while offering a primer on what can reasonably be expected from personalized medicine.

Richard Burkhardt - Darwin is known as the father of evolutionary biology, but the University of Illinois’ Burkhardt gave a convincing argument that he was also instrumental in establishing the field of animal behavior and behavioral ecology.

Eugenie Scott - The cultural/historical half of the conference was equally fascinating, including this talk by the executive director of the National Center for Science Education debunking Darwin myths (including his “deathbed confession”) propagated by creationists.

Michael Ruse - The funniest talk at a Darwin conference may sound like a backhanded compliment, but Ruse’s irreverent refutation of 2009’s trend of “Darwin was Wrong” articles is full of chuckles, while making a convincing argument for Darwin as skilled aggregator and communicator.

Hopi Hoekstra - Where many of the weekend’s lectures took the 30,000-foot view of Darwin and evolutionary biology, Harvard’s Hoekstra presented an elegant case study of evolution in motion with her field study of beach mice and coat color.

There’s also a long list of one-on-one interviews with the conference participants that I haven’t waded into yet.

The second treasure trove of science videos, linked in passing yesterday, is the library of lectures from last year’s MacLean Center for Clinical Medical Ethics seminar series. Some of the most interesting conversations in science and medicine take place over ethical questions, an assertion this series proved again and again. On the blog, we covered transplant ethics in China, the disclosure of HIV test results in India, relief efforts in Indonesia and Haiti, the bright side of spiraling health care costs, the involvement of doctors in Guantanamo Bay interrogations, and the general challenges of global health programs at American medical centers.

Now, you can go beyond our analysis with videos of the actual lectures, made available by the University of Chicago’s Global Health Initiative. Despite the lure of free lunch, I couldn’t make it to all the lectures, so I look forward to catching up in advance of this year’s series starting next month (pdf schedule).

What infectious disease causes the most deaths in the United States? Most would probably guess HIV, or after last year’s H1N1 scare, influenza. But the deadliest infectious disease in our country is actually MRSA, the antibiotic-resistant form of Staphylococcus aureus sometimes referred to as a “Superbug.” Nearly one percent of the U.S. population is colonized with MRSA, and infection with the bacteria causes more than 100,000 hospitalizations and nearly 20,000 deaths each year.

What’s worse, MRSA is incredibly hard to treat, as its name suggests. For the last three decades, hospitals have seen more strains of S. aureus resistant to methicillin and similar antibiotics, and some strains have even shown resistance to vancomycin, the current last resort antibiotic. Even when a MRSA infection is successfully cleared, it has a high rate of relapse, as unlike other infections the body does not acquire immunity after the initial attack. A vaccine against the bacteria would thus be a valuable medical tool, a protection to prevent the infection from establishing a foothold.

Two recent papers from the laboratory of Olaf Schneewind, professor and chair of microbiology at the University of Chicago, offer promising strategies for how such a vaccine would work. We talked about Schneewind’s research back in April, when he presented the story of the MRSA vaccine search to the MacLean Center for Clinical Medical Ethics (video here). The new papers demonstrate the first signs of success for those strategies, with protection against the insidious bacteria seen in animal models.

One strategy, published today in the Journal of Experimental Medicine, turns one of MRSA’s most dangerous weapons against itself. Proteins on the cell surface of each MRSA bacterium help trick the cells of the body’s immune system into holding off their attack, and even helping to disperse the bacteria to other organs. Immune cells called B cells typically attach to surface proteins to generate specific antibodies that recruit “killer” T cells to attack the intruding infection. But when those B cells bind a MRSA surface protein called Protein A, a chain reaction leads to B cell death rather than antibody creation.

Schneewind and his colleagues decided to try to turn the tables once more against MRSA by using Protein A as the key component of a vaccine strategy. Critical genes for Protein A’s interaction with B cells were genetically scrambled, creating a non-toxic form of the protein that loses its deadly influence over the immune system. Instead, exposing animals to this neutered Protein A allows the immune system to generate protection against the normal Protein A, such that subsequent infection with MRSA is blunted. Mice injected with the modified Protein A and then later exposed to MRSA strains that cause infections in the US and Japan exhibited fewer bacterial abscesses and reduced mortality compared to control mice.

“I believe that Protein A may be the key to making a staphylococcal vaccine,” Schneewind said.

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Many neurological disorders struggle with the same problem as their cousins, the psychiatric disorders: a fuzziness of diagnosis. Even well-known diseases such as Parkinson’s and Alzheimer’s are tricky for physicians to diagnose, since their hallmark symptoms (dementia, or movement issues) show up late and can reflect any number of conditions with different treatment strategies. Meanwhile, the subjective elements of diagnosis for a disease like autism can produce even more confusion, particularly in parents wanting the best care for their child.

The hope is that, someday, diagnosing Alzheimer’s or autism will be as simple as running a quick test that says Yes or No. Two studies this week produced excitement that physicians are nearer to such a goal, but also revealed how difficult it will be to obtain such a definitive answer. The coverage of the papers also revealed the importance of carefully reading the results of testing the test, knowing the difference between the testing terminology of “sensitivity” and “specificity.”

The most glaring example of this confusion was over a paper announcing a new biomarker test for Alzheimer’s Disease in the journal Archives of Neurology. Here, a group of scientists used an interesting technique to find the best way to predict Alzheimer’s disease from a spinal tap test, working from a data set of hundreds of patients with Alzheimer’s, mild cognitive impairment, or no dementia. With an unbiased analysis, the researchers determined thresholds for two markers involved in the pathology of Alzheimer’s (beta-amyloid and tau protein) that successfully predicted a diagnosis of Alzheimer’s from the spinal tap alone. This “sensitivity,” the ability to make the correct diagnosis in someone who has the disease and avoid false negatives, was reported at impressive levels of 94 to 100 percent.

However, news reports mistakenly said that the new biomarkers were a “100 percent accurate” test for Alzheimer’s. As many blogs have already pointed out, that’s just not, well, accurate, and in fact obscures the most interesting part of the study. As reported by the authors, the biomarkers misidentified about one-third of “control” subjects, that is patients who showed no signs of dementia or impairment, as being positive for Alzheimer’s. That’s a pretty low “specificity,” since it means the test generates significant false positives. But are they really false? The authors also report preliminary results that “there was a tendency for more progression to MCI in cognitively normal subjects with the AD feature,” meaning that people who were normal at baseline, but showed biomarkers for Alzheimer’s, may be on the cusp of developing symptoms of the disease. The “wrong” answers might just be the most useful answers, drawing attention to people on the verge of developing Alzheimer’s, a population that may be helped more by early treatment.

Another neurological condition where an early, clear diagnosis would be very helpful is autism. The current psychiatric means of diagnosing autism may be the main driver of its steadily increasing rates, a fact which has caused some to wonder whether those guidelines are specific enough, and whether autism is even one single disease at all. Rather than basing the diagnosis on interviews and psychiatric assessments, some are working towards genetic or imaging techniques that can give more definitive answers on autism.

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A medical residency is no walk in the park. For a resident, there are no weekends, and working 9 to 5 is a half-day. Working overnight is routine - every 3 or 4 nights on some rotations - and entails more than just the “graveyard shift,” as a typical on-call shift can run from 7 in the morning to 1 in the afternoon…the next day.

In 2003, pushback from patient groups and politicians led the Accreditation Council for Graduate Medical Education (ACGME), the body that oversees U.S. residency programs, to institute limits on duty hours. Residents were restricted to working 80-hour weeks, limited to 24 hours of continuous care (with a 6-hour extension allowed for some activities), and were supposed to receive an average of one day off for every seven days.

Hospitals initially struggled to adapt to the new restrictions, redrawing schedules and hiring support staff to cover for the missing resident hours. But just when things were settling down, another round of restrictions is growing imminent, this time fueled by studies showing that being awake for longer than 16 hours is equivalent to having a blood alcohol level of 0.05 percent. Last year, the Institute of Medicine recommended that residents be restricted to 16-hour shifts, or be required to take a mandatory 5-hour nap if they work more than 16 hours. The panel also recommended additional supervision, particularly of interns, the first-year residents just out of medical school.

An ACGME task force subsequently softened the restrictions, limiting the 16-hour rule to interns. A public comment period for those guidelines just ended, but most medical centers are already assuming that they will be put in place next summer unchanged and are planning accordingly. I spoke to two University of Chicago Medical Center faculty members who supervise residency programs - Terrance Peabody, chair of orthopedic surgery, and Vineet Arora, associate professor of medicine - about how hospitals are preparing for the changes.

How do you feel about the new ACGME recommendations?

“The real issue is that, in surgery culture, taking care of someone for 24 hours is a big part of the learning experience,” Peabody said. “It’s important that residents undergo following somebody through that period of time. The concept of making a surgeon a shift worker goes against the real culture of surgeons, who feel obligated to provide some continuity of care, and whose tasks aren’t easily delegated the way they are in internal medicine.”

“I think it’s a very tall order for medicine especially given the value of following patients through the night,” Arora said. “I can also understand it’s a reasonable compromise between what ACGME had to balance, which was the fact that there was a public pressure to reduce hours amid the data about fatigue, as well as still preserving the opportunity for residents to work overnight and follow patients.”

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The structure of the agitoxin-Shaker channel complex (from Benoit Roux lab webpage)

Scientific grants are usually given out one investigator at a time, funding a single laboratory’s research. But as the questions of science grow larger, and the technology needed to answer those questions grows ever more specialized and expensive, funding collaborative grants becomes increasingly common practice. One type of multi-investigator grant has been dubbed a “glue” grant, so named because it sticks together researchers from several different institutions for the common pursuit of one important science goal.

Today, the National Institute of General Medical Sciences announced a glue grant on the topic of membrane proteins, an effort that will be led from right here on the University of Chicago campus. The grant formally creates the Membrane Protein Structural Dynamics Consortium, a team of nearly 30 scientists from 14 institutions in the United States, Germany, Canada, and the Netherlands.

“We have been able to put together almost a dream team of people currently involved in this type of research,” said Eduardo Perozo, PhD, Professor of Biochemistry and Molecular Biophysics at the University of Chicago Medical Center and the leader of the team. “There has been nothing like this project before.”

Membrane proteins are the machines on the factory floor of the cell’s surface, tasked with letting materials in and out of the cell, responding to signals from other cells, and even producing energy. The family includes ion channels that Perozo (and fellow team member Benoit Roux) study, the receptors for neurotransmitters and hormones, and various other pumps, transporters, and exchangers. Figuring out how these miniature machines function will be extremely helpful in designing new drugs, both to treat diseases caused by defective membrane proteins and for improving drugs that rely upon membrane proteins to get to their target.

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