Since it’s one of those days where I feel like one of the few people working a full day, I’ll keep the links brief. Regular programming will resume next Tuesday.

1) You can set your watch by the timing of the predictable backlash to major scientific announcements, particularly in this age of instant internet vetting. Much of the immediate criticism tends to focus on how the media handled/exaggerated the scientific finding; i.e. the transition of my twitter feed’s take on J. Craig Venter’s “synthetic life” from enthusiasm to calling him “the Paris Hilton of science.”

But the more interesting wave takes place months later, when publications rebutting the original journal article begin appearing. This week, that slower wave crashed against last year’s unveiling of Ardi, the 4.4-million-year-old partial skeleton argued to be a human ancestor by its discoverers. Today in Science, the same journal that published the original paper, two groups attempt to chip away at the conclusions surrounding Ardi - whether the species lived in a woodland habitat and where it falls on the human family tree, closer to us or apes. Science allowed the original authors to respond to both comments, and the New York Times and the San Francisco Chronicle played the role of referee.

2) The Gulf of Mexico offshore oil spill continues unabated, and the major journals are both doing a nice job of explaining the scientific aspects of the story without getting mucked up in the politics. Science has dedicated a page to their spill coverage, where I found this interesting article about the oil-eating bacteria of the ocean (and how BP’s dispersants might interfere with their natural activity). Nature’s page features posts from a reporter on the research ship Pelican, which was in the Gulf studying the effects of the spill earlier this month. To explain the “top kill” strategy employed yesterday by BP to plug up the oil spill, CNN turned to esteemed scientific communicator Bill Nye the Science Guy. Thus far, the top kill clog appears to be working; let’s hope it stays that way.

3) Mars Phoenix RIP. The Knight Science Journalism Tracker has a roundup of obituaries written for the NASA Mars probe, which was officially declared inoperable this week. Charlie Petit also raises a good question: was it really a success? Often, space projects are given the benefit of the doubt because of the wonder they inspire, but the high cost of such efforts mean they should receive just as much, if not more, scrutiny than other scientific experiments.

4) The increased risk-taking behavior of younger siblings is illustrated with a real world example: stolen bases by baseball players.

5) And finally, celebrate the opening of beach season with this excellent article by my former Tribune colleague Joel Hood about how scientists are developing new methods of measuring and forecasting harmful bacteria in Lake Michigan. Good to see science on the front page in Chicago.

Scientists will be the first to admit that science sometimes makes mistakes. Though debates and changing theories are often seized upon by everyone from anti-vaxxers and climate change skeptics as flaws in the scientific process, the constant revision is actually the key to science’s strength, gradually building accuracy through trial and constructive error. Still, it’s frustrating when a particular biomedical theory fails to pay off in the clinic, and more so when additional data spins the entire theory around.

Such a reversal may have occurred this week with the publication in Nature of a cancer research paper by University of Chicago and Northwestern University scientists. The research project, a collaboration between the laboratories of Marcus Peter (now of Northwestern University Feinberg School of Medicine) and Ernst Lengyel, looked at CD95, known to be one of the cellular “death receptors.” That intimidating nickname comes from CD95’s role in apoptosis, the self-destruct mode triggered by a cell when it is damaged or under attack.

If CD95 was so good at killing cells, it followed that activating the receptors would be a potential strategy for treating cancer, where the problem is unrestrained cell division and resistance to apoptosis. But the new Nature study finds evidence for the mirror image of that conclusion: Activating CD95 actually fuels the growth of cancer cells.

“This is a paradigm-shifting discovery,” said Lengyel, associate professor of medicine at the University of Chicago Medical Center. “For 20 years, scientists have tried to use CD95 to kill tumors, but what we showed is that it is actually promoting tumor growth.”

With laboratory experiments conducted on cell lines and mouse models of cancer, the research team showed repeatedly that cancer growth was slowed by removing or inhibiting CD95, not activating it. That explains a mystery that has always hurt the original CD95-cancer theory: if the receptor is so deadly to cancer cells, why do they express so many of them? The researchers concluded that the function of CD95 must somehow turn traitor when cells become cancerous, flipping a death receptor into a growth receptor. As an accompanying editorial by Douglas Green of St. Jude’s Children’s Research Hospital said, CD95 is a “wolf in wolf’s clothing.”

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A critical step in the design of any clinical trial is picking the right primary endpoint, the result that will usually make or break the study. That’s more difficult than it sounds - one’s hope is to cure a disease or relieve a patient’s symptoms, but choosing the best specific measure for those goals is something of a guessing game. Further, the process can be made even more difficult for diseases that do not have a long history of clinical research and thus no established endpoints.

Idiopathic pulmonary fibrosis, an unexplained and very serious scarring of the lung tissue, is one such disease. Because of the extremely poor prognosis for patients with IPF, where most patients die within five years of symptoms first appearing, no large-scale clinical trials were tried until 1999, said Imre Noth, Associate Professor of Medicine at the University of Chicago Medical Center. Even today, some groups of IPF patients are still left out of clinical trials.

“The area that has been neglected by far and away are the severe patients,” Noth said. “The rationale beyond most biologics that have been looked at is you need to start early to make an impact.”

But the results of a promising clinical trial of a new treatment for severe IPF patients was published last week in the New England Journal of Medicine. The bad news? The primary outcome chosen for the study - improvement in a patient’s walking distance during a 6-minute test - failed to improve in the group treated with drug. Nevertheless, the trial was greeted with an optimism unusual for the IPF field, Noth said, thanks to a silver lining of secondary successes and promising near-misses.

“This has been a very frustrating disease for pulmonologists,” said Noth, a member of the Idiopathic Pulmonary Fibrosis Clinical Research Network, which designed and administered the trial. “The sense is, ‘Finally something we can give to our patients,’ because at least you can make them feel better, which is a great first step.”

The drug itself is an interesting story. Called sildenafil, it has already been marketed by Pfizer under the name Revatio as a treatment for pulmonary arterial hypertension. But most readers probably know sildenafil by its other commercial name: Viagra. The drug’s more famous use was actually an unintentional side effect, as it was originally developed to be a hypertension treatment. Trying sildenafil for IPF is going back to those primary intentions, capitalizing upon the drug’s ability to improve blood supply to the lungs.

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Occasionally, drugs produce beneficial mysteries - effects that are useful to physicians despite being largely unexplained. Levodopa (L-dopa), the most commonly-used treatment for the symptoms of Parkinson’s disease, is meant to replace dopamine, the neurotransmitter lost as the disease progresses to its most severe stages. Clinicians recognize that the benefical effect builds up slowly over weeks despite the same dose of medication. In addition, after a patient’s L-dopa is stopped, the relief of a patient’s motor symptoms can persist partially for weeks, long past the time it takes to clear the drug entirely from one’s system. Though this effect has a name - the “long duration response,” or LDR - nobody’s quite sure what causes it, though physicians are happy to put it to use in patients.

Adding to the mystery is the fact that animal models of Parkinson’s disease, usually involving chemical brain lesions, have consistently failed to replicate the long duration response. But in a bit of serendipity, a University of Chicago laboratory studying the role of dopamine in the learning of motor skills may have unintentionally found the LDR in a mouse. Published this month in the Annals of Neurology, the finding could dramatically shift both the theory and treatment of Parkinson’s.

Jeff Beeler, a postdoctoral researcher in the laboratory of Xiaoxi Zhuang, associate professor of neurobiology, wanted to study a difficult problem: how can one untangle motor performance from motor learning? The deficits seen with Parkinson’s disease, such as muscle tremors and akinesia (the inability to initiate movement), implicate dopamine as an important part of the brain’s motor control. But is it simply that one needs dopamine to move, or do you need dopamine to learn how to move? It’s a hard question to experimentally test, Beeler said.

“If you can’t perform something, in a sense you can’t learn it,” Beeler said. “On the other hand, if you can’t learn it you can’t perform it. It’s a chicken and egg thing.”

So Beeler began working with a unique mouse strain, called aphakia mice, with a naturally-occurring genetic mutation. The mice were first known for being blind (aphakia means the loss of the lens of the eye), but were later found to have a severe, 90 percent depletion of dopamine neurons - similar to the loss seen in advanced Parkinson’s patients. But strangely, these mice exhibit only very subtle motor deficits.

“It’s a good model of particular aspects of Parkinson’s disease,” said Un Jung Kang, professor of neurology and director of the University of Chicago Movement Disorders Center and another author of the paper. “The simple way of saying it is that this is a model of very mild Parkinson’s disease that reflects a lot of endogenous compensation. They basically have a very minor deficit in terms of motor performance.”

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Last October, a group of Illinois legislators visited the University of Chicago Medical Center for two days of education and discussion about cardiovascular medicine and health care reform, part of a nationwide “Legislator in the Lab” program. In addition to laboratory tours and panel discussions, the legislators and their staffs heard a series of brief, informative lectures on different cardiology topics, from prevention of sudden cardiac death to the use of stem cells for heart tissue regeneration. Many of these lectures were videotaped and posted to the Medical Center’s YouTube channel, and I thought I’d share a couple of them here today.

Dr. Matthew Sorrentino on Risk Factors for  Cardiovascular Disease

Everyone knows a little bit about risk factors for heart disease, such as obesity, age, family history, and tobacco use. But it’s important to remember that these factors don’t exist in isolation - instead, they interact in a way that can dramatically increase a person’s risk for heart attack or stroke. As such, cardiologists keep a scoresheet on their patients, adding up risk factors to determine a patient’s risk for heart attack. Matthew Sorrentino, professor of medicine in the section of cardiology, breaks down how doctors use these risk assessments, and how they can guide interventions that offer fast, powerful risk reduction.

Dr. Rupa Mehta on Heart Disease in Women

The undisputed leaders in the arena of women’s health awareness are breast cancer organizations, which routinely organize charity walks and fundraisers that draw thousands of participants and light city buildings pink. But as Rupa Mehta, assistant professor of medicine in the section of cardiology, reminded the audience in her talk, breast cancer and other diseases trail far behind cardiovascular disease as a killer of women. 460,000 women in the United States die from heart disease each year, which breaks down to about one death a minute. Mehta talks about the challenges that face physicians and patients in recognizing and treating heart disease in women, including watching out for the different set of symptoms - including fatigue, sleep disturbances, and shortness of breath - that signal an oncoming heart attack in females.

The newborn. (courtesy: J. Craig Venter Institute)

The biggest science story of the year may have broken yesterday, though it’s hard to say either the topic or the source was a surprise. J. Craig Venter, one of the driving forces of the Human Genome Project, announced via the Institute that bears his name the creation of the first synthetic cell - a bacterium with DNA entirely constructed in the laboratory. Mycoplasma mycoides JCVI-syn1.0 might not have the catchiest of names, but it’s a landmark of scientific achievement: the first time man has moved beyond studying life to creating it.

The paper, published yesterday in Science, is a technical marvel of laboratory perseverance. It turns out creating a genome from scratch isn’t as easy as just sticking a bunch of nucleotides together; the final string of more than 1 million base-pairs had to be laboriously constructed from hundreds of smaller cassettes, and even the tiniest errors could be catastrophic. “Our success was thwarted for many weeks by a single pair deletion in the essential gene, dnaA,” the article reports (and you can almost feel the frustration). “One wrong base out of over one million in an essential gene rendered the genome inactive.”

There’s no doubting the magnitude of the achievement, but is Venter’s creation truly “synthetic life,” as many media outlets are ready to claim? Some interesting perspectives are provided in Science’s rival Nature, who asked several scientists and ethicists to write essays on the meaning of the announcement. Steen Rasmussen from the University of Southern Denmark argues that it is not truly synthetic life, because the Venter’s team created only the DNA, which was placed into a pre-existing, natural cell. Another expert, Jim Collins from Boston University, calls the synthetic genome a “stitched-together copy of the DNA of an organism that exists in nature, with a few small tweaks thrown in.” Indeed, the Venter genome is built from 300+ bacterial genes the group determined to be the minimal amount necessary to create a functional cell, with the only significant addition being “watermarks” left by the researchers (including quotes from Richard Feynman and James Joyce).

But if science is like crossing the Atlantic Ocean one lily pad at a time, Thursday’s announcement was still a pretty damn cool lily pad. The ultimate dream - of creating new life that can generate fuel, clean up pollution and produce faster, better vaccines - may still be years if not decades away from reality. So too, may be the ultimate fear of human-created organisms running wild in the natural ecosystem. As Carl Zimmer wrote in 2007, with just the right mixture of awe and caution, about the future of synthetic biology, someday “out of a million garages, a million new species may bloom.”

Blog founding father Jeremy Manier covered Venter’s project back in 2008 for the Chicago Tribune.

Elsewhere…

I never get tired of hearing about the story of Phineas Gage, the 1800’s railroad worker who suffered a particularly gross brain injury and came away with a radically altered personality. The damage to his frontal lobe helped scientists figure out the role of that brain region in controlling impulses and behavior. But a new article, highlighted on Mind Hacks, finds evidence that Gage showed signs of recovery from his injury later in life, adding both a new chapter to a favorite psychology-class story and testimony to the brain’s ability to adapt after even the most extreme injury.

Speaking of brain trauma, A new JAMA article reports that patients who have suffered a traumatic brain injury are almost 8 times more likely to experience depressive symptoms after the injury. Joseph Fink, an assistant professor of neuropsychology at the University of Chicago Medical Center, weighed in on the findings with MedPage Today. The study reminded me of a poster I saw just last week presented by medical student Maxwell Rovner at the Pritzker Senior Scientific Session, where a smaller study of epilepsy patients found very high rates (88%) of depression in the 72 hours after a seizure. Clearly, any shock to the brain can lead to severe psychiatric consequences on top of the more direct neurological issues; if the mechanism for those disturbances could be unraveled, it could say a lot about the origins of mental illness.

I can barely wrap my mind around the scale of the Gulf oil spill disaster, so I’ve taken refuge in stories that emphasize the scientific angles of this environmental story. Here’s a nice NatureNews piece on the use of dispersant chemicals, a strategy I’ve seen a lot of skepticism about on my news feed. An AP story explains why it has been so hard to get a firm grasp of the size and spread of the oil spill. Of course, even the science surrounding the oil spill gets political, as yesterday’s New York Times reported.

Nothing like a good scientific explanation for a paranormal phenomenon. In this case, it’s ball lightning, which two physicists theorize could be the result of stroke-induced tiny magnetic fields that produce hallucinations.

Markus Boos, winner of the Best Basic Science Research Poster award. (photo by David Christopher)

Medical students are busy people. Whether they’re working through phonebook sized texts their first two years or learning to navigate the hospital halls over the last two years, free time is at a premium. So when a medical student makes room in their busy schedule for a research project, it’s a commendable feat of calendar gymnastics.

It was inspiring then to see so many fourth-year Pritzker School of Medicine students presenting at last week’s Senior Scientific Session, the 64th annual event celebrating student research projects. One month shy of convocation, the students delivered oral and poster presentations that covered a diverse range of science, from racial disparities research to structural protein chemistry to cancer drug discovery to computational diagnostic algorithms. It’s hard to find a common thread through such far-flung approaches, but it’s clear that a significant portion of the medical school class is interested in both practicing medicine and pushing it forward.

Of course, a little friendly competition also spices up the event, and eight of the 9 speakers and 38 posters received awards for their efforts. Judged by a panel of medical school faculty, students were split into non-PhD and MD/PhD groups for fairness; the latter group, part of the Medical Scientists Training Program, get an extra few years to conduct their research. Projects were also divided into clinical and basic science pools, reflecting a student’s choice of the laboratory or the clinic as their research setting.

Even the basic science studies had one eye on the clinic, however. Luke Miller, who won the Franklin McLean Medical Student Research Award for “the most meritorious research,” presented an example of 21st century cancer drug discovery: select a target and screen thousands of molecules for promising activity. Miller chose the homologous recombination pathway, sort of a DNA repairman for cells when they experience genetic damage. Cancer cells, Miller said, are thought to be “addicted” to this pathway, making some tumors resistant to treatment with radiation or chemotherapy drugs. After screening 9,000 molecules, Miller and his colleagues found a molecule, dubbed sb-3, that inhibits an important step in DNA repair. Combining sb-3 with pre-existing drug and radiation therapies may restore the sensitivity of stubborn tumors to treatment, Miller theorized.

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At the end of April, an FDA approval marked the end of a long regulatory road for an interesting drug with an even more interesting history: Provenge. Though it’s usually described as a vaccine for metastatic prostate cancer, that terminology is a bit misleading, as unlike traditional vaccines it doesn’t work by exposing an individual to an inactivated virus or a protective antigen. Instead, Provenge is more accurately the first “activated cellular immunotherapy,” a treatment where a patient’s own white blood cells are modified in a laboratory and re-infused to attack tumor cells. Though scientists have pursued this strategy for years, Provenge is the first product to reach the market after a tumultuous path that involved three separate randomized clinical trials.

Now that Provenge has been approved, a slow rollout of the treatment will begin in medical centers and urology clinics around the country. In the Chicago area, the University of Chicago Medical Center will be the first to offer Provenge, though treatment slots will initially be limited as the company behind the treatment, Dendreon, ramps up their capacity. Because of the press attention on the treatment’s novel mechanism, its controversial past, and the questions surrounding its slow debut, I visited with Russell Szmulewitz, an instructor of medicine who treats and studies prostate cancer for a Q&A session on Provenge.

Q: How does Provenge work?

A: Provenge is an activated cellular immunotherapy, which is a complicated way to say it is using your body’s own immune cells to target and fight your cancer. The process is labor-intensive, because it involves a process called apheresis, where patients are attached to a machine that’s sort of similar to a dialysis machine. But instead of cleansing your blood, it takes the white blood cells out of the blood and gives you back the red blood cells. Those white blood cells are then sent to the manufacturer at Dendreon, exposed to an activating protein, called PAP, which is a protein made by most prostate cancer cells, attached to a white blood cell growth factor called GM-CSF. The fused protein is incubated with the cells together, and what’s left is an activated cell product that’s called sipuleucel-T. That’s then shipped back to the treating physician and infused like a transfusion. The whole process is repeated every two weeks, for a total of three times.

It’s the first of its kind in terms of active immunotherapies. It’s not really a vaccine per se; a vaccine typically means injecting a patient with a protein and then your body has an immune response to that protein. This is quite different in that the cells are taken out of your body, futzed with, and given back to you.

Q: Who is Provenge meant for?

A: The label will be for minimally symptomatic, castrate-resistant, metastatic prostate cancer patients. These are patients who have failed standard hormonal manipulation, which we call castration, and have minimal symptoms from their disease. Obviously, that’s a bit subjective, but the studies that were done with this product were not done with patients who had severe pain from their malignancy or severe weight loss or things of that nature.

So if the patient fails hormonal therapy and then fractures a bone and has severe pain from their disease, this product is probably not indicated. That doesn’t mean it wouldn’t help them, we just don’t know, because that’s not the type of patient that was included in the studies. That being said it’s a huge population of patients.

Q: Why should doctors and patients be excited about Provenge?

A: It’s pretty non-toxic. Other than the fairly complicated apheresis procedure - 3 to 4 hours hooked up to this machine with a large IV - there’s really few, if any, severe toxicities. Some common things people get are fevers, chills, headaches, but that’s pretty much it in terms of side effects.

Because it’s a less-toxic, immune-based therapy, it’s gotten a lot of press. We’re excited because it works. It’s nice that it has limited toxicity, that’s for sure, but it seems to work.

In this disease state, it’s incurable. In fact, metastatic prostate cancer in general, even hormone-sensitive metastatic prostate cancer is incurable, so anything at this point in the game to improve quality of life, prolong life, meaningful life, those are the metrics you are judging success or failure by. It’s the first active cellular immunotherapy in cancer and especially in solid tumor malignancy, and it has a very different side effect profile than your typical cancer therapy.

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Venomous animals such as snakes, scorpions and spiders are typically the stuff of phobias for most people. But the toxins those creatures have developed to immobilize and kill their prey are actually some of nature’s most finely-tuned weapons, sharpened by millions of years of evolution to hit a particular molecular target. For Zoltan Takacs, an Assistant Professor at the University of Chicago Medical Center, it’s those qualities that have made snakes and venom a life-long source of fascination, not fear. From expeditions around the world to catch and collect tissue from venomous animals to laboratory experiments that seek to unlock the potential of those toxins for research and clinical use, Takacs has turned a childhood love of creepy-crawlies into a career.

Acknowledging Takacs’ unique existence as half-scientist/half-adventurer, National Geographic today announced him as one of their 2010 Emerging Explorers. With 13 other award recipients, Takacs earns $10,000 to put toward expeditions that have already taken him to over 130 countries in pursuit of venomous species. Takacs brings tissue from those animals back to Chicago for further study, looking to repurpose the venomous tricks of nature into highly-selective ligands that could have therapeutic value.

“It’s a straight connection between rain forest and lab bench,” Takacs said last week, from a snake-free conference room in Hyde Park. “Nature is not limited to the African savannah with elephants and lions. There is also the underlying molecular biodiversity, and if that’s erased then we lose the potential for new drugs.”

That potential is vast: Takacs estimated that 10 to 20 million different toxins exist in nature. Only 10,000 or so of those toxins have been discovered, and of those only 500 have been thoroughly studied. But from the small supply of well-characterized toxins, at least 12 drugs have already been derived and are currently in use for treating blood pressure, heart failure, heart attacks, and diabetes.

“If you face a heart attack in the United States and go to the emergency room, there are three drugs for emergency treatment and two of them are derived from snake venom,” Takacs said. “These are truly lifesaving drugs.”

Finding more drugs means cataloging more toxins, so Takacs teamed up with biophysicist Steve Goldstein, Professor of Pediatrics and an expert on ion channels, to create libraries of toxins based on templates obtained from nature. A recently published example from Takacs’ research is a vivid demonstration of how those toxins can be reshuffled by scientists to create new compounds even more specific - and potentially useful in the lab and clinic - than their natural counterparts.

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Lauren Sallan and Michael Coates in the lab (photo by Jason Smith)

In the Devonian Period of roughly 400 million years ago, fish were the masters of Earth, filling the seas and rivers with enormous diversity from the 30-foot-long Dunkleosteus to lobe-finned fishes like the modern lungfish. Then, 359 million years ago, something happened. The fossil record tells a clear before-and-after story: Dunkleosteus and its family members, the placoderms, disappear, and the ray-finned fishes that we currently think of when we think about fish went from underdog to dominant. Shortly thereafter, a few survivors figured out how to crawl onto land, and the rest was vertebrate history.

For paleontologists, extinction events are the chapter markers in the story of life, marking profound shifts in the course of evolution. Scientists have long focused on one such marker occurring near the end of the Devonian Period: the Kellwasser Event, considered one of the “Big Five” extinctions in Earth’s history. But evidence for the Kellwasser Event 374 million years ago was based on invertebrate fossils such as clams and mussels, which are abundant and easy to find. The vertebrate fossil record of the time, consisting largely of fishes, is less complete, making it difficult to do the detective work necessary to pinpoint a critical extinction event.

That is, until now, when Lauren Cole Sallan and Michael Coates applied analytic techniques from the field of ecology to a richer dataset of vertebrates fed by recent fossil discoveries. The research, published today by the Proceedings of the National Academy of Sciences, looked at the pattern of vertebrates in the late stages of the Devonian Period, and found a different chapter break - not at the Kellwasser Event, but at the “Hangenberg Event,” 15 million years later.

What’s more, the global species shakeup that resulted from the Hangenberg Event would set the stage for the evolution of all modern vertebrates, including humans. By significantly reducing the species pool, the extinction created a bottleneck effect that allowed a small set of survivors to re-diversify and re-populate.

“There’s some sort of pinch at the end of the Devonian,” said Coates, professor of organismal biology and anatomy at the University of Chicago. “It’s as if the roles persist, but the players change: the cast is transformed dramatically. Something happened that almost wiped the slate clean, and, of the few stragglers that made it through, a handful then re-radiate spectacularly.”

“Everything was hit, the extinction was global,” said Sallan, a graduate student and lead author of the paper. “It reset vertebrate diversity in every single environment, both freshwater and marine, and created a completely different world.”

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Last month, we told you about a new cardiac defibrillator device that was implanted for the first time in the United States here at the University of Chicago Medical Center. That procedure - performed by Martin Burke, professor of cardiology, on 38-year-old mother of four Brooke Bergeron - was also the first of a global clinical trial that hopes to test the subcutaneous implantable cardioverter-defibrillator (S-ICD) in more than 300 people. But a new medical device doesn’t just jump straight to the world-testing stage; the current trial was built on the foundation of several smaller trials that worked out the kinks of the device and proved its effectiveness in smaller pools of patients.

The data from those trials were published this week in the New England Journal of Medicine, and portray an instructive case study in how a new device is developed and tested without endangering the patient. In trials conducted in New Zealand and Europe over the last 10 years, different configurations of the device were compared, software was refined, and a slow, careful roll-out of the S-ICD in more and more patients was achieved. With a majority of successes along the way, the researchers set the stage for the wider testing of the device currently in progress while exciting many in the field of cardiology.

“This could be a game changer, if indeed this is the direction this technology goes,” Richard Page, president of the Heart Rhythm Society, told Bloomberg News.

Interestingly, the first step was an engineering challenge - figuring out the best configuration for the device’s leads, which both sense the heart’s rhythms and deliver the shock if necessary. The classic implantable defibrillators have an advantage in this respect, since the leads are actually placed inside the heart. But with subcutaneous leads placed under the skin near the sternum, the same task can be accomplished from farther away with a stronger, but still safe, shock. All the same, the device’s designers wanted to minimize the amount of electricity required to reset the heart’s rhythm, and thus tested four different configurations (pictured above) to find the one that performs its function with the least firepower.

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Six months ago, some of the world’s brightest evolutionary biologists and scholars gathered on the University of Chicago campus for a three-day birthday party celebrating Charlie Darwin’s 200th. At the time, the blog featured live-ish coverage of the event wherein I tried my best to capture the fascinating lectures and discussion on display at Rockefeller Chapel and Ida Noyes Hall. But if my words were insufficient, you can now watch a handful of videos from the conference, courtesy of the official website. The videos are not embeddable, but here’s a quick viewer’s guide.

Jerry Coyne (University of Chicago): “Speciation:  Problems and Prospects”

The author of Why Evolution is True discussed where he and Darwin disagree: the answer to the very title of Darwin’s seminal On the Origin of Species. Coyne explains the debate between sympatric and allopatric speciation, and how barriers - physical or otherwise - are usually the cause of new species formation.

Paul Sereno (University of Chicago): “Dinosaurs: Phylogenetic Reconstruction from Darwin to the Present”

Famed fossil hunter Sereno brought along the second-oldest bird skeleton ever found, but turned his focus from bones and digs to how morphologists - scientists who study the physical characteristics of specimens - can keep pace with the geneticists in constructing the Tree of Life.

David Jablonski (University of Chicago): “Paleontology and Evolutionary Biology: The Revitalized Partnership”

Speaking of paleontology, Jablonski pointed out how Darwin pointedly avoided using the fossil record in his classic writings because of its many holes and gaps in the mid-19th century. Today, fossil remains of species such as the bivalves that Jablonski studies provide scientists with a “trail of mayhem, destruction and heartbreak” that can be useful in reconstructing evolutionary history.

Neil Shubin (University of Chicago): “Great Transformations in Life: Insights from Genes & Fossils”

Shubin traveled to the unforgiving environment of the Canadian Arctic to make the landmark discovery of Tiktaalik, the earliest-known limbed tetrapod fossil. But the majority of his talk focused on the more comfortable setting of the laboratory, where genetic experiments on how limbs develop in sharks and skates offer clues to human evolution.

Robert J. Richards (University of Chicago): “Darwin’s Biology of Intelligent Design”

Co-organizer Richards represents the more historically and culturally-inclined upper half of the conference, presenting the provocative claim that Darwin believed natural selection to be a purposeful force rather than a blind machine of nature. ScienceLife founding father Jeremy Manier wrote about Richards’ lecture here.

There’s no such thing as a perfect drug. Physicians know that for every treatment benefit a drug provides, there will also be side effects that must be taken into consideration. Ideally, these side effects can be controlled with careful dosing of the drug or close monitoring of the patient, such that the drug’s good side can be maximized while its potential toxic effects are minimized. But because every individual patient will respond to a given drug in a different way, that balance is easier said than done.

As such, the guidelines for dealing with common side effects of a particular drug aren’t always obvious, especially when the drug in question is new or its side effect is atypical. That was the case recently with a class of drugs called angiogenesis inhibitors, the first of which was approved in 2004 for cancer treatment. Angiogenesis inhibitors, such as bevacizumab and sorafenib, were developed to be more tolerable cancer drugs than the classic chemotherapy agents known for having several difficult side effects. But these drugs - which act by blocking the growth of new blood vessels around a tumor - presented with a potentially dangerous side effect of their own: hypertension. Studies found that anywhere from a quarter to 72 percent of patients given one of the these angiogenesis inhibitor drugs experienced elevated blood pressure, with the effect occasionally severe enough that the drug had to be stopped.

But as a cancer-fighter, these drugs have been very successful. So a panel, including two University of Chicago Medical Center physician-researchers, was convened by the National Cancer Institute to come up with recommendations for physicians eager to use angiogenesis inhibitors in cancer patients but concerned about the potential for hypertension. Led by Michael Maitland, assistant professor of medicine, and George Bakris, professor of medicine, the 13-member panel released their findings this month in the Journal of the National Cancer Institute. The purpose, the researchers said, was to reassure physicians that a promising new drug class can be safely used if certain precautions are taken.

“If carefully managed, I think these drugs are a huge move forward in our armory against cancer,” said Bakris, who directs the Medical Center Hypertensive Diseases Unit.

That a cardiologist such as Bakris was involved in a discussion of how to best use a cancer drug reflects the broad approach taken by the panel. Cancer drugs are most often prescribed by - you guessed it - cancer specialists, for whom hypertension is generally not a primary concern. By bringing oncologists and cardologists to the table together, Maitland said that the panel was able to come up with guidelines that satisfied both specialties and made sure the patient was being treated for both diseases. As a result, physicians can feel more comfortable treating treating patients with angiogenesis inhibitors even if they have a history of hypertension, or are at elevated risk for high blood pressure due to age, family history or diet.

“Often the case is those patients aren’t seeking medical attention for hypertension until they find that they have a tumor and need treatment for cancer,” Maitland said. “If a patient is hypertensive, a physician should not dismiss that as irrelevant just because they have advanced cancer. We already know that ignoring co-morbidities in a cancer patient can generate as much risk for their long term survival as the stage of the cancer.”

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General internal medicine might seem like an awfully vague term. But assuming the health care reform bill signed by President Obama in March will be fully implemented, the general internists will finally have their day. Many of the bill’s provisions are focused on a reshuffling of the American medical landscape, which is currently dominated by sub-specialists focused on one organ system. In recent years, fewer medical students have chosen to pursue lower-paid and less glamorous careers in internal medicine, leaving a worrisome shortage in primary care doctors and hospitalists just as 32 million uninsured Americans are about to go on the books. The spotlight is about to focus on internal medicine.

“About time,” would probably be the response from most of the doctors assembled in Minneapolis last week for the 2010 Society for General Internal Medicine national meeting. Over three days, thousands of internists met in discussion groups and research panels to chart the course for a new age of American medicine. Though some fears were expressed about how an already overwhelmed system would be able to deal with the new influx of patients, the conference was more focused on seizing the opportunity to rehabilitate U.S. primary care and bring medical services to those who are traditionally underserved. The urgency of the moment was expressed right in the caps-lock and exclamation point of the meeting’s theme: “Value(s)-based generalism: THE TIME IS NOW!”

Of course, many of these efforts to expand the net of primary care didn’t start when Obama used 22 pens to sign the health care bill on March 23rd. Many of the presentations by University of Chicago faculty at the conference discussed pilot programs already being tested to improve the care of those who have traditionally fallen through the health care cracks, efforts to reduce disparity that may be instructive as the reform measures fall into place.

A workshop moderated by Marshall Chin, professor of medicine, presented four examples of programs funded by Finding Answers, Chin’s Robert Wood Johnson Foundation-supported group for studying racial and ethnic health disparities. Chin said the mission was to “evaluate interventions that reduce racial and ethnic disparities,” and the short presentations showed the breadth of that mission. Projects using cultural awareness training, electronic medical record software, and pay-for-performance programs were all discussed as potential solutions, with researchers from Harvard, Brigham and Women’s Hospital and Baylor outlining projects currently underway. One fascinating approach, described by Barbara Turner from Penn, employed African-American patients who had successfully controlled their high blood pressure as “peer coaches” to help fellow patients struggling to adhere to treatment - an elegant way of using community bonds to spread healthy messages.

Another successful example of community health intervention was presented in tandem by Deborah Burnet, section chief of internal medicine at the Medical Center, and Lorri McClinton-Powell, a teacher from Woodlawn Elementary School on the southeast side of Chicago. Last year, Burnet and colleagues conducted a pilot study of the POWER-UP program, an anti-obesity effort based around after-school activities for children and parents, with 40 children and their parents at Woodlawn. Fourteen weekly sessions - focused on themes such as “Muscle Mania” and “Stop & Shop” - taught the children about healthy eating, exercise, and behavior at restaurants and grocery stores. Though small, the study’s results held promise, with declines in overall body mass index among all but the heaviest kids at baseline. The group is currently working with Chicago Public Schools on the possibility of expanding the program for a larger study, Burnet said.

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Climate Scientists to Politicians: Enough Already

A pretty remarkable letter was published in the journal Science this week, signed by 250 members (including4 University of Chicago scientists) of the National Academy of Sciences and calling for “an end to McCarthy-like threats” surrounding climate change. The letter makes a stand for reason on both climate change specifically and science in general, arguing that the scientific process of constantly questioning and improving the knowledge of a particular subject should not be misinterpreted as flaws.

When someone says that society should wait until scientists are absolutely certain before taking any action, it is the same as saying society should never take action. For a problem as potentially catastrophic as climate change, taking no action poses a dangerous risk for our planet.

The letter comes on the heels of Oklahoma Sen. James Inhofe suggesting in March that U.S. and British scientists should be criminally investigated for their role in the “ClimateGate” hacked e-mails incident. Michael Mann, the Penn State climatologist who created the famous hockey stick graph showing the recent rise in global temperatures, was cleared by his university of any misconduct charges, but was targeted this week by Virginia Attorney General Ken Cuccinelli. Such efforts are political grandstanding at its most despicable, and seriously endanger the ability of scientists to conduct research in an open and unpolitical forum. Great coverage, as always, by Andrew Revkin at Dot Earth.

2010 BIO Coverage Roundup

To wrap up BIO week, I thought I’d cast a net for some of the other commentary from this week’s conference in Chicago. Bruce Japsen of the Chicago Tribune saw part of Al Gore’s speech and focused on how the global recession wounded the biotechnology industry. Tuesday’s keynote session with George W. Bush and Bill Clinton was controversially closed to the media, but Forbes ran a perspective on the event from a conference attendee. Industry magazine Fierce Biotech and the San Diego Biotechnology Network were also grinding out gavel-to-gavel coverage alongside our own.

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