Science Life - A blog of news and ideas in Biomedicine

Rewriting the Book on the Brain

Posted at 7:46 am CT on August 31, 2011

medical-neurobiologyStudents might sometimes think that their textbook appeared out of thin air, the accumulated knowledge of a field spontaneously forming into a heavy slab of facts and figures. But textbooks are like any other type of book, with flesh-and-blood authors who labor over the words within and make a million tiny decisions to shape the final product. If you try to include everything, the book will likely be too heavy for even the most determined or muscular students to carry. Cut too much out, and your definitive textbook might be scorned as incomplete and elementary.

In writing her new textbook, professor of neurobiology Peggy Mason helped find the happy middle by starting with a very specific audience in mind: the medical students that she has spent 15 years teaching at the Pritzker School of Medicine. Her completed product, simply named “Medical Neurobiology,” is the first designed with aspiring physicians in mind, teaching med students about the broad influence of the central nervous system. Picking a specific target audience helped Mason make the hard choices about what to include and what to leave out, she said - even if the final 660 pages is heavier than she intended.

“I think it’s actually the only textbook completely aimed at the medical students,” Mason said. “I did a few things because of that that no other textbook does.”

For starters, Mason chose not to interpret “medical neurobiology” as simply “neurology.” Only a small percentage of medical students will eventually choose to train as neurologists, but the other 97 percent also need to be familiar with the central nervous system, she said. Knowing the anatomy and function of the brain, spinal cord, and nerve pathways can help everyone from future neonatologists measuring infants’ reflexes to future pulmonologists treating asthma to future geriatricians looking for the warning signs of dementia or motor deficits.

Another important decision came to Mason after a dinner with four medical students who gave her insight into the overwhelming workload of an aspiring doctor.

“All of a sudden I just realized that the immensity of the knowledge base that they need to acquire in two years,” Mason said. “It made me think anew about what we were teaching them, and I decided that as entertaining as it may be for us to talk about the newest, greatest research, it’s a disservice to them. They don’t have the time; they need the body of information that they need clinically and not the extraneous stuff. So I tried to cut out as much as I could.”

Mason kept the page count down by restricting the coverage wherever possible to topics of clinical relevance, leaving out popular neuroscience textbook subjects such as the fundamentals of smell and leech swimming (a common model for the neurobiology of locomotion). Instead, she focused on the anatomical regions where patients are most likely to suffer lesions that cause symptoms, and the neurotransmitter imbalances that cause behavioral changes. Pop-out boxes describe the clinical manifestations physicians are likely to see, such as the pupil constriction and droopy eyelid of Horner syndrome, which indicates damage to a specific pathway from the brain to the eye.

But to really help important neurobiology topics take up permanent residence in the minds of medical students, Mason deployed an armory of inventive examples and metaphors to make the text both enjoyable to read and memorable.

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Posted by - Rob Mitchum

Linkage 7/8: Eyes on the Prizes and More

Posted at 11:22 am CT on July 8, 2011

shrine-21

By John Easton

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

This is a great honor - and a storage problem.

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

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

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

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

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

Elsewhere…

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

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

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

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

Posted by - John Easton

Linkage 3/18: Match Day, Podcast #0.3, and More

Posted at 10:52 am CT on March 18, 2011
Photo by Bruce Powell

Photo by Bruce Powell

Yesterday wasn’t just St. Patrick’s Day for fourth-year medical students around the country - it was also Match Day, the tense and celebratory day when aspiring doctors learn the residency program where they will spend their next 3-7 years. At the Pritzker School of Medicine, green-clad students and supporters absolutely packed the hospital’s Billings Auditorium for the big event Thursday morning, cheering their peers as they were called one by one at random to collect their match envelope. In a local tradition, it literally pays to go last, as students throw into an informal prize pot for whoever has to wait and squirm the longest to pick up their envelope (second-to-last gets a Hershey bar as consolation). In the video below, you can see some of that process - including the outcry when the last envelopes are miscounted - followed by the amazing tension-release of the countdown and unison envelope opening.

The numbers from the day are just as exciting as the video. At Pritzker (recently ranked #12 among medical schools by US News and World Report), 110 students were matched in 24 specialties at 46 institutions, including 23 students who will stay with us here at the Medical Center. The most popular specialties for Pritzker students were internal medicine (25% of the class), general surgery (11%), and pediatrics (11%). Nationally, trends continued to shift for the second consecutive year toward primary care specialties such as internal medicine, family medicine, and pediatrics, according to the National Residency Matching Program, a step in the right direction to meet some of the increased demand for primary care doctors expected in the wake of health care reform. MedPageToday’s Kristina Fiore breaks down the numbers.

Podcast 0.3: Transplants, Rock-Paper-Scissors Ecology, and More

We have settled on a name for our young research podcast: Bench to Bedside. However, we are still keeping the training wheels on as we work out the technical kinks and explore the best ways to deliver audio versions of our latest research and medical stories. Please enjoy the third installment of our podcast, featuring a recent coast-to-coast kidney transplant chain that involved the Medical Center, how Rock-Paper-Scissors can explain biodiversity, the fight against indoor air pollution in Nigeria, and the new numbers on the eating disorders epidemic in the United States. As always, we would love to hear feedback on what we’re doing right and wrong at robert.mitchum@uchospitals.edu or dianna.douglas@uchospitals.edu.

Bench to Bedside Episode #0.3 by robmitchum

Elsewhere…

Some people keep ant farms, some people keep multiple flasks of bacteria growing for 13 years (and counting) to study evolution. Ed Yong writes about experiments from Michigan State University that show “tortoise” bacteria can beat out “hare” bacteria over the long run. (And if you’re a science communicator of any sort, do listen to Ed and Carl Zimmer’s “Death to Obfuscation” session from January’s Science Online meeting)

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Posted by - Rob Mitchum

Linkage 1/21: Science Online, Kinect Surgery, & More

Posted at 9:49 am CT on January 21, 2011

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Last weekend, I was one of the fortunate 300 who gathered in Research Triangle Park, North Carolina for the 2011 edition of Science Online. The simplest way to describe Science Online is as a science blogging conference, but the real topic on the table was the broad future of science communication, be it through blogs, podcasts, ebooks, twitter, or plain old paper. Through “unconference” sessions led by panels but driven by audience discussion, workshops, field trips to labs and museums, and good old-fashioned bar conversation, scientists, journalists, and scientist-journalists dissected how science can be best defended and explained in a time where mass media coverage is increasingly scant or poor.

I could spill literally thousands of words on what I learned and discovered at Science Online, but for the sake of my audience, I’ll restrict myself to three subjects most relevant to an academic medical center in the new media environment. For more coverage, see the Columbia Journalism Review’s 30,000-foot view, Ed Yong of Not Exactly Rocket Science on the science-blog echo chamber, and Chris Rowan at geology blog Highly Allochthonous on the elephants of the conference. Or you can wade through the over 10,000 tweets sent from and about the conference.

1) Patients Can Blog Too

The majority of the bloggers who attended Science Online cover science through the lens of peer-reviewed research, government policy, or media criticism. Many of these blogs deal with the long-term picture: how will this laboratory study impact medical treatment in 10 years, or how will climate change policy affect our planet’s future. But a corner of the science-writing world is written by people particularly engaged in what science can do for them immediately: patients fighting serious disease.

As a session on “Patient Blogging as Therapy” proved, social media is a natural fit for patients to share information and support. Dave deBronkart, known on the web as e-Patient Dave, called in via Skype to talk about how his own fight against advanced kidney cancer exposed him to the online world of patient engagement, including the technically-primitive but still-functioning listservs of ACOR. Now, having beat his cancer, he’s the hub of an electronic patient advocacy community that includes other panelists like David Seidman (blogging about his kidney disease and need for a transplant) and Alberto Rocca, who started a website for families of children with the rare lung cancer pleuropulmonary blastoma. deBronkart’s motto of “potent information simply portrayed empowers people” was an inspiring reminder of a different way people use blogs or any other media at their disposal to seek knowledge and truth, and the opportunity for online conversations about health that are two-way streets.

2) A Calm Voice in a Shouting Match

But where will patients, of the blogging or non-blogging sort, receive that potent information? The internet is all about easy access to info on virtually any topic, but the quality of that information often leaves much to be desired. Like the search engine TV commercial, a simple search can be easily drowned out by nonsense and falsities - often, in the case of medical advice, dangerous ones. The magnitude of this problem could be read from the beleaguered company accurate medical information kept in the “Defending Science Online” session: evolution and climate change, two other areas where misinformation very noisily tries to shout down evidence-based knowledge.

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Posted by - Rob Mitchum

Linkage 12/10: Imagination Dieting, Arsenic Update, Cold Hands

Posted at 11:19 am CT on December 10, 2010

submarine_sandwich

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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Posted by - Rob Mitchum

Life on Arsenic?

Posted at 9:28 am CT on December 8, 2010
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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.”

503457main_arsenic_fullA 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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Posted by - Rob Mitchum

Linkage 10/8: The Nobels, ADHD, and Spoofs

Posted at 8:27 am CT on October 8, 2010

alfred_nobelThis past week has been Nobel Prize week, and while none of the winners so far have had a University of Chicago connection (unlike last year’s trio), it’s still good fun for science spectators. Trying to divine a common theme from all of a year’s winners is probably futile - the selection process at the Royal Swedish Academy of Sciences is still pretty mysterious, and doesn’t seem to follow any consistent logic in the laureates it spits out. This year, the Thomson Reuters predictions - considered by many to be the best - have produced an ohfer so far, despite throwing out anywhere from 4-7 names for each of the prizes. The 2010 list is typically scattershot, with a mix of established science and science with yet unrealized potential; the only theme I can pick up is “non-American.”

Medicine: Occasionally, the Nobel committee is accused of waiting too long to award a prize. This year’s award in physiology or medicine, awarded to British scientist Robert G. Edwards for his work on in vitro fertilization, may fit that charge. The first baby produced by IVF procedures developed by Edwards and colleague Patrick Steptoe was born more than 30 years ago, on July 25, 1978. Since then, over 4 million “test tube babies” have been born to parents who would not otherwise have been able to have children. It’s kind of amazing, then, that the leaders of IVF had not previously been awarded the Nobel Prize - and sadly, Steptoe did not live to receive the honors, having died in 1988 (Nobel rules forbid posthumous awards). According to media reports, Edwards himself is in poor health and was unable to grant interviews about winning the award. Of course, the Vatican had its own criticisms of the winners.

Physics: Rather than rewarding a scientific discovery several decades after the fact, this award was given to science that, according to many experts, hasn’t yet ripened. Russian scientists Andre Geim and Konstantin Novoselov were recognized for the development of graphene, an extremely thin and extremely strong material thought to be useful in everything from solar panels to satellites. The emphasis is on “thought to be,” because the material was only discovered in 2004, and has yet to be incorporated into a commercially available product. Interestingly, the main gripe here was that it may have been more appropriate for the chemistry Nobel rather than the physics prize. Geim also notably becomes the first scientist to win both the Nobel Prize and its illegitimate brother, the Ig Nobel Prize, which he won for his research on levitating frogs.

Chemistry: If this were a fairytale, this prize would seem to be not too stale, not too fresh, but just right. Richard Heck, Ei-ichi Negishi, and Akira Suzuki each have an organic chemistry reaction that bears their name, and are considered to have laid important early groundwork for the burgeoning field of molecular engineering. The trio invented and refined the art of “palladium-catalyzed cross-coupling,” which finds a way to stick formerly contact-shy carbon atoms together. While the process is not exactly a household name, its impact is felt in medicine cabinets around the world. “Cross-coupling methods are now used in all facets of organic synthesis, but nowhere more so than in the pharmaceutical industry, where they are used on a daily basis by nearly every practicing medicinal chemist,” organic chemist Eric Jacobsen told ScienceNOW.

Elsewhere…

In the same issue of Archives of General Psychiatry where Daniel Le Grange’s study of family-based anorexia treatment was published, another Medical Center study probed the link between ADHD and teenage suicide. A study of 125 children diagnosed with attention deficit hyperactivity disorder between 4 and 6 years of age were three times as likely to attempt suicide between ages 9 and 18, compared to a control group of non-ADHD children. “The importance of this study is simply that it confirms that ADHD in children is not something to take lightly,” lead author Benjamin Lahey, professor of epidemiology, told WebMD.

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Posted by - Rob Mitchum

Linkage 8/27: Chronic Fatigue & Oil Spill Messiness

Posted at 12:15 pm CT on August 27, 2010

virus_leteomasisChronic 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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Posted by - Rob Mitchum

Linkage 8/13: The Headache of Brain Testing

Posted at 8:28 am CT on August 13, 2010

26638mediumMany 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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Posted by - Rob Mitchum

Finding Cancer Risk in a Gene Desert

Posted at 12:04 pm CT on July 13, 2010

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The Human Genome Project has had a rough year, from a PR perspective. To mark the 10th anniversary of the completion of a “working draft” for the human genome, many media outlets have chosen the “what have you done for me lately?” angle in assessing the project’s impact upon everyday medicine. Outlets such as the New York Times, The Economist, and The Guardian all ran articles about the as-yet-unfulfilled promises of the Human Genome Project in finding new cures for a wide range of diseases, a reality far from the “complete transformation in therapeutic medicine” promised in 2000 by Francis Collins.

One prominent area of frustration has been with genome-wide association studies (GWAS), which compare a population with a particular disease such as atherosclerosis or lung cancer with a healthy population to identify genes associated with disease risk. Many of the “hits” from these studies offered confusing results; as Nicholas Wade wrote in the Times: “most of the sites linked with diseases are not in genes - the stretches of DNA that tell the cell to make proteins - and have no known biological function, leading some geneticists to suspect that the associations are spurious.”

But Marcelo Nobrega, assistant professor of human genetics at the University of Chicago Medical Center, disagrees with that conclusion. And in a paper published today in the journal Genome Research, Nobrega’s laboratory demonstrates how these “non-genetic” GWAS hits can have dramatic biological effects significant for disease risk.

“The alternative, which we’ve known for a while now, is that the genome is not only comprised of genes,” Nobrega said. “Only one percent of the genome becomes proteins, but there are these regulatory elements everywhere that have important biological roles but are not protein-encoding sequences. Mutations in these proteins presumably will lead to disease or increase the risk of disease, there’s no reason to believe otherwise.”

The paper, authored by Nobrega with Nora Wasserman and Ivy Aneas, demonstrated this principle by tracking down a GWAS hit associated with cancer of the prostate and other organs. Studies identified a segment on the 8th chromosome that was associated with an increased risk of cancer, but it pointed to a region that contained no protein-encoding genes - a stretch known as a “gene desert.” In previous work, Nobrega’s team had tracked down small regulatory elements within these deserts that help choreograph the expression of genes for the development of organs. The new search had the opposite mission: to find not the regulatory elements that build an organ, but the elements that could someday send cell growth awry in those organs.

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Posted by - Rob Mitchum

ASCO 2010: Two Productive Singles

Posted at 7:12 am CT on June 7, 2010

ASCO Name Tag Logo Black SIn the New Yorker last month, Malcolm Gladwell wrote elegantly about the euphoria and frustration of cancer drug discovery. Tracing in parallel the path of a modern biotechnology company and a team of doctors in the 1950’s, Gladwell illustrated the unexpected twists and turns that mark every new drug’s journey from laboratory to clinic, in a game where the stakes are literally life and death. The dramatic scene that Gladwell chose to open his piece? The American Society of Clinical Oncology meeting, a huge gathering of cancer researchers where the highly-anticipated results of clinical trials for the next wave of promising anti-cancer agents are presented in a flourish of success or a sigh of failure.

The ASCO meeting this year is being held in Chicago, whose McCormick Place is one of the few convention centers gargantuan enough to hold tens of thousands of researchers from around the world. Throughout the Escher-like hallways of that building, echoes of Gladwell’s opening scene were taking place, with Kaplan-Meier curves - the graph that shows differences between the drug-treated group of patients and the control group - delivering their positive and negative verdicts. Over the weekend, two success stories featured University of Chicago involvement; both were exciting small steps in the battle of science against different types of cancer.

One of the most difficult to treat cancers is also one of the most common: lung cancer, which is newly diagnosed in more than 200,000 people a year in the United States. Lung cancer researchers, including Ravi Salgia of the University of Chicago Medical Center, have been looking for proteins that are behaving badly inside lung cancer cells and that may represent promising targets for cancer therapy. One such target, the enzyme anaplastic lymphoma kinase or ALK, is overactive in a small percentage of lung cancer patients due to a chromosomal translocation - a break in the DNA that produces a dangerous Frankenstein protein called EML4-ALK.

While only 4 percent of patients with lung cancer are positive for EML4-ALK, the mechanism suggests that an inhibitor of the protein may be effective in attacking cancer in that population. Sunday, researchers (including Salgia) presented evidence of that strategy working - an inhibitor of ALK called crizotinib successfully controlled lung cancer in 90 percent of patients enrolled in a small trial. In 57 percent of the patients, tumors actually shrank - an incredible advance in a cancer that is nearly always untreatable. The authors said that a larger, Phase 3 trial is already underway to verify the findings in a larger population.

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Posted by - Rob Mitchum

Linkage 5/7: Climate Change McCarthyism & Neanderthal Sex

Posted at 10:09 am CT on May 7, 2010

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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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Posted by - Rob Mitchum

BIO Conference Digest - Valleys of Death

Posted at 11:30 am CT on May 6, 2010

img00261-20100505-11062Three days and 7,500 words later, I’m happy to be back at my office desk this morning after an exciting week at the BIO conference. For those of you without the time to wade into the coverage, here are some concluding thoughts and a selection of links to the most memorable parts of the meeting. If you want the real-time rundown, click for the coverage from Monday, Tuesday, and Wednesday.

I’ve never been to a conference quite like BIO. The ivory tower of academia is fortified enough that your typical scientific conference operates somewhat insulated from real-world dollars and cents, other than the constant calls for funding and the lavish laboratory supply displays on the exhibit floor. But at BIO, the world’s largest biotechnology conference, the conversation starts with business. Pharmaceutical companies advertise their wares, startups network with venture capital companies, countries and states tout their locale as fertile for biotech business, and countless panels discuss the impact of the world economy on the industry. The marketplace focus creates a different vibe, to say the least - from presentations handicapped by non-disclosure agreements to a significantly fancier dress code to audience questions that sound more like a shareholder’s meeting than a research seminar.

Those are not necessarily negatives - I only mean to point out how it was all a bit foreign to a former academic scientist such as myself. If nothing else, the emphasis on the bottom line produced more focused research talks - the science, in most cases, was expected to provide a concrete solution, not incremental progress. Biotechnology is a field vaguely-defined enough that those solutions were broad and ambitious: medical treatments, devices, and tests dominated the discussion, but there was also talk of ending world hunger with bio-engineered agriculture, rolling back climate change with biofuels, and protecting the world from misuse of biotechnology with biosecurity biotechnology. If occasionally one felt like the speaker was selling their science rather than presenting it for discussion - well, yeah, they were.

img00257-20100505-1103But with all the discussion of promising technologies for the future, the main obstacle appeared to be fairly low-tech: human communication. Many sessions hoped that the bright side of the global recession would be more partnerships between academic research centers and private companies, with industry helping academic scientists bridge “the valley of death” in commercialization while academia fills the gap created by industry R&D cuts. But the language barrier between the two entities doesn’t seem to be weakening, as evidenced by any panel where representatives from industry and university sat side by side. Disconnected motivations (profit vs. tenure), approaches (basic science vs. applied science), and pacing (quarterly reports vs. multi-year grant cycles) all would seem to make the academia-industry bridge an especially difficult construction project.

The other communication breakdown oft lamented at the conference was between the industry and the public. Any time a field comes together, an us vs. them mentality quickly forms - the sense that nobody but us understands just how critically important neuroscience or dentistry or insurance actuary is to the world. But biotechnology has its own battles to fight, after journalists and politicians have targeted products such as corn ethanol fuel and genetically-modified crops for reasons both valid and uninformed. Michael Specter, staff writer for the New Yorker, rightly said that many attacks against biotechnology are borne of unsubstantiated fear caused by scientific illiteracy. But Specter also criticized pharmaceutical companies for shooting themselves in the foot by being cagey with the press, sitting in “defensive crouches” rather than emphasizing the good things they do. A relevant lesson for a conference where media were blocked off from keynote addresses by George W. Bush, Bill Clinton, and Al Gore, save for access during the first five minutes of the latter speech.

But criticisms aside, I had a great time covering the conference. The enthusiasm of the scientists - be they from industry or university - was infectious, and the motivations of all involved are pure despite the smell of profit. The full potential of science can’t be realized if it is kept within laboratory walls, and while the process of distributing science to the greater public can be messy, it is absolutely critical if we are to improve the world around us. Here’s a roundup of the favorite things I saw this week.

img00253-20100505-1100The Gee Whiz Sessions

Building New Tissue with Nanotech

Stem Cells from Skin Outpace Stem Cells From Embryos

Artificial Pancreas? There’s an App for That

University of Chicago at BIO

The Chicago Innovation Pipeline

Translational Research Forum: Forging Better Partnerships and Making Trials Faster

Why Better Diagnostics Need a Better Health Care System

The Business Side of BioTech

The United States’ Narrowing Biotechnology Lead (ft. CNN’s Fareed Zakaria)

Surviving the Recession (post by Karla Melendez)

Biotechnology Battlegrounds

Improving the Science of Regulation (ft. FDA Commissioner Margaret Hamburg)

The Arms Race of Biotechnology

The Ethics of Engineering Nature

Posted by - Rob Mitchum

Linkage 4/23: Bill Gates & Swine Flu’s Birthday

Posted at 6:42 am CT on April 23, 2010
Bill Gates walks across the University of Chicago campus April 20, 2010. (Photo by Jason Smith)

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

A College Dropout Returns to Campus

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

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

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

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

A Year of Swine Flu

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

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Posted by - Rob Mitchum

Linkage 3/24: The Pinky of An Ancestor and Harmful Neurologisms

Posted at 10:54 am CT on March 26, 2010

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Expanding the Human Family, One Cave at a Time

A couple weeks back on the blog, Callum Ross debunked a lemur-like creature, Darwinius masillae, purported by some to be a very distant human ancestor. If you were feeling sad about this contraction of the human family circle, you may have been cheered by news this week about the potential debut of a new, more human-like human ancestor. There is no fancy Latin name for this relative yet, because even the authors of the paper announcing its existence are unwilling to declare that an entirely new species has been found. But it’s enough to dream up some not entirely unscientific (and somewhat unsettling) daydreams of a time when what we know today as humans were not the only two-legged tool-using primates on the scene.

The uncertainty surrounding the finding published in Nature by Johannes Krause, Svante Paabo and colleagues is that the discovery was made with a little bit of paleontology and a lot of genetics. The human ancestors or cohabitants we’re more familiar with - like Neanderthals or Homo erectus - were discovered in skeleton form, the classical way scientists learn of extinct creatures. But Krause & company’s fossil findings are limited to a pinky bone discovered in a Siberian cave, dated to 40,000 years ago. Because you can’t tell much anatomically from a pinky bone, the researchers instead harvested DNA from the bone; specifically, mitochondrial DNA (mtDNA), a smaller stretch of genes inherited entirely from one’s mother. When compared to mtDNA from modern humans and Neanderthals, it was dramatically different from both species - roughly twice as different as the gap between humans and Neanderthals.

The authors (and most of the outside scientists I’ve come across online) reason that the most likely explanation for that difference is that the pinky belongs to a very old human-like species, one that may have branched off from modern humans 1 million years ago. There are other theories - Carl Zimmer proposes one alternate theory built on the rather salacious premise of interspecies lovin’ - but analysis from the nucleus DNA of the proposed new species is necessary to decide. In the meantime, it’s fascinating to think about a time when humans sort of like us had to compete with Neanderthals and whatever this new ancestor may have looked like for resources, much like different species of birds will fight over territory and food.

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Posted by - Rob Mitchum