Sen. Dick Durbin tours Argonne National Laboratory with Rick Stevens, Professor of Computer Science (photo courtesy of Argonne)

In Washington, the fight over budget cuts is well underway, as a Republican majority in the House and a Democratic majority in the Senate tussle over the best way to reduce a multi-trillion dollar federal deficit. The first bill of the new House, H.R.1, set federal appropriations for the rest of fiscal year 2011 (ending in September) and snipped $61 billion from the budget, predominantly from discretionary domestic spending. One target of those cuts would be the National Institutes of Health budget, which would lose roughly $1.6 billion of its $32 billion budget for funding scientific research in the United States.

As you might expect, this news was not welcomed by Chicago-area researchers, who turned up in lab coats to support a news conference by Sen. Dick Durbin last Sunday at Northwestern University’s downtown campus. Durbin vowed to fight against the cuts as H.R.1 is discussed in the Senate, saying that interrupting the funding would slow progress toward new treatments for diseases such as AIDS, diabetes, and cancer. (video here)

“When you put these research projects on hold, you can’t ask the laboratory mice to take a nap,” Durbin said. “You can’t ask the cultures to stop growing - we’ll get back to you at the end of the fiscal year. And you can’t expect the professional researchers, the men and women who have dedicated their lives to medical research, to have certainty that next year they’ll have a job.”

Researchers from each of the major Chicago academic hospitals appeared at the conference and talked about how the proposed budget cuts could harm their own projects. Michelle Le Beau, director of the University of Chicago Comprehensive Cancer Center, discussed the biomedical research underway at UChicago thanks to the nearly $300 million in NIH funding received this year and last. Le Beau focused in on her own research examining therapy-related acute myeloid leukemia - a “very cruel and ironic” cancer caused by the chemotherapy and radiation treatment of a prior tumor. Any job losses that follow from NIH cuts could break up the expert team she has formed to study causes and treatment of the disease, she said.

“A lapse in funding will result in dismantling our highly specialized research team, and this leads to a loss of capability, because it takes years to assemble these teams again,” Le Beau said. “These are individuals who have trained for years to apply their extraordinarily unique skills. They have families to support and bills to pay.”

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ScienceLife ran 219 posts in 2010, and choosing the best of them is as hard as picking a favorite gene.  So here’s a month-by-month scan of a busy year at the University of Chicago Medical Center, full of exciting discoveries in the laboratory and the clinic. The impact of some of this research is already being felt by patients receiving improved, evidence-based medical care. For other studies, the clinical benefit may be years in the future, and may take unpredictable forms. As a closing message for 2010, we’ll re-quote the recently departed Eugene Goldwasser, whose laboratory research isolating and purifying the hormone erythropoietin has helped millions of people worldwide.

“It is a particularly impressive example of how basic research can pay a dividend that could not be anticipated at the start,” Goldwasser wrote about his life’s work, “and it is a pity that the lesson still has not been learned by those who control public funding of science.”

January: Tong Chuan-He looked at how cancer may result from cells who don’t want to grow up. Scientists studied how sleep affects the language learning skills of starlings (with painstakingly acquired video of the experiment!). Richard Jones combined two laboratory staples - Western blots and DNA micro-arrays - to develop a new method for studying protein networks. While physicians such as Tammy Utset treat patients with lupus, UChicago scientists are looking for the genetic origins of the autoimmune disorder.

February: Many Medical Center employees returned from volunteering with relief efforts in Haiti, and we filmed video interviews with Rex Haydon, Tiffany Cupp, Richard Cook, and Dima Awad on their experiences. Most of the human genome is “junk” between protein-encoding regions, but Marcelo Nobrega developed a way to find important regulatory elements in that genetic sea. Like birds, human learning can be affected by sleep, and Leila Kheirandish-Gozal reported on the impact of obstructive sleep apnea upon learning in children. Can a single protein in the brain create behaviors associated with drug addiction in rats?

March: Everyone knows air travel is stressful, but did you know that eastbound flights cause stronger cortisol changes than westbound trips? The laboratory of Milan Mrksich found a way to direct stem cells to form fat or bone by shaping them into stars or flowers, a brilliant example of bioengineering. Computational neuroscientists discovered how touch is like vision in the brain, knowledge that could be used to someday re-engineer Luke Skywalker’s robot hand. Dartmouth president and Partners in Health co-founder Jim Yong Kim visited to talk about a new, needed area of research: health care delivery.

April: Researchers at the Field Museum and the University of Chicago teamed up for the Emerging Pathogens Project, an effort to find new viruses in animals before they jump to humans. Cardiologist Martin Burke tested out a new type of internal defibrillator device that can go under the skin, instead of into the heart (the clinical trial, reported in May, was a success). In a lecture to the MacLean Center of Clinical Medical Ethics, transplant surgeon J. Michael Millis described his efforts to bring American organ transplant practices to China.

May: A trial testing the erectile dysfunction drug Viagra for a rare, untreatable lung disease failed, but pulmonologist Imre Noth found a silver lining. Lauren Sallan and Michael Coates uncovered evidence of a previously unappreciated mass extinction event 360 million years ago that changed the path of life on Earth. Researchers from the University of Chicago and around the world presented science at the frontier of biotechnology at the annual BIO conference.

June: In a study that is literally the size of an entire country, epidemiologist Habibul Ahsan measured the toll of a tragic, accidental exposure of millions to arsenic in Bangladesh. Putting a gene from fireflies into the pancreas of mice isn’t mad science, it’s an imaging tool that will help study cures for diabetes. Epigenetics, the modifications that turn genes on and off, took off in 2010, and cardiologists Stephen Archer and Jalees Rehman linked one epigenetic factor to pulmonary artery hypertension.

July: Scientists don’t often get to see the fruits of their research in the flesh, but the Celebrating the Miracles gathering of diabetic children weaned off injected insulin thanks to genetic research was a moving exception (video of the event can also be viewed). Another hot topic in science and medicine this year was the use of computational analysis to sift through rapidly accumulating data, topics explored by Gary An and Andrey Rzhetsky. Or you can build a computer model of a brain network to study the dynamics of epilepsy, like neurologist Wim van Drongelen.

August: Air pollution is a problem indoors as well as outdoors in developing countries where dung and firewood are used to cook food - a problem being tackled in a project led by Sola Olopade. A study of the hormonal changes induced by a stressful test revealed a surprising protective effect of marriage and long relationships. Microbiologist Olaf Schneewind’s laboratory developed two new strategies against MRSA, the most-wanted cause of hospital-acquired infections.

September: To study multiple sclerosis, neurologist Brian Popko’ s laboratory developed a new mouse model that can replicate the disease, then spontaneously recover. Meanwhile, a new drug to treat MS, originally isolated from fungus found in wasps, was approved by the FDA and is being studied for broader uses at the Medical Center. The micro-organisms that live in humans were analyzed as part of a “microbiome” study looking at the protective effects of breast-feeding against a intestinal disease.

October: Common wisdom on quitting smoking says to stay away from cigarette-associated cues, but research from psychiatrist Harriet de Wit’s laboratory revealed that abstinence could make craving even worse. A study of how getting a good night’s rest affects dieting results suggested that “sleeping off the pounds” isn’t merely a fantasy. Graduate student Daniel Matute solved a 100-year-old riddle about how quickly new species become reproductively incompatible with each other.

November: In perhaps our favorite study of the year, geneticist George Perry found a way to acquire the genomic information of endangered species from…poop. The evolutionary biologist Leigh Van Valen passed away, but his Lewis Caroll-inspired Red Queen Hypothesis lives on. Sometimes statistics don’t tell the whole truth, as in the curious case of the aspirin paradox - why the cardio-protective drug may actually predict worse outcomes after heart attack.

December: Evolution textbooks may need a rewrite after geneticist Manyuan Long’s laboratory discovered that new genes can be just as essential as old genes. A study by neurobiologist Nicholas Hatsopoulos proved that the only thing better than a thought-controlled device is a thought-controlled device equipped with a robot arm. Ripped from the headlines: microbiologist Jack Miller weighed in on the hype over arsenic-based bacteria, and ethicist/physician/friar Daniel Sulmasy discussed the Presidential Bioethics Commission’s report on synthetic biology.

All told, it was a great year of science and medicine. Let’s do it again in 2011! Regular posting will resume Jan. 3rd. Happy Holidays.

It’s great to have a treatment that’s proven to work in a difficult psychiatric condition such as anorexia nervosa. It’s even better to have two treatments for such a disorder. But having multiple options also creates a quandary for psychiatrists: with a new patient, which treatment do you try first? Creatures of habit like the rest of us, many doctors will simply stick with the method they know best until given convincing evidence that it’s worth switching gears. To be the new treatment of choice, a method must beat out the current champion in a head-to-head battle.

One such comparison, conducted by researchers at the University of Chicago Medical Center and Stanford University, was published yesterday afternoon in the Archives of General Psychiatry. The trial compared the most common form of treatment for adolescents with anorexia, known as adolescent-focused therapy (AFT), with the newer, family-based treatment (FBT), also sometimes known as the Maudsley Approach. The latter name comes from the Maudsley Hospital in London, where Daniel Le Grange, now director of the Eating Disorders Clinic at the University of Chicago, helped develop a new approach to bringing anorexic teens back to healthy weight and eating habits.

Under adolescent-focused therapy, the therapist works directly with the patient on a one-to-one basis, emphasizing the importance of weight gain and helping them accept personal responsibility for healthy eating. Family-based treatment, as you might expect from the name, does more to incorporate the parents into that process, equipping the patient’s mother and father with the tools to encourage healthy eating at home. By doing so, the therapist hopes to avoid hospitalizing the patient while permanently adjusting the home environment, removing factors that could lead to relapse after therapy is completed.

“No one is more available to care for the kids than the parents are; no one would put the time aside in the way that parents would, and no one loves their kids more than parents do,” Le Grange told NPR’s Morning Edition (where you can also hear the perspective of one patient’s mother on family-based treatment).

The two therapies had been compared previously, but in smaller studies with only two or three dozen patients. True convincing evidence requires a randomized trial, with enough patients for the statistics to make a strong case for one of the treatments. So, combining forces between Chicago and Stanford, Le Grange and his collaborator, James Lock at Stanford, were able to gather 120 patients with anorexia nervosa (with an average age of 14-1/2) for the study.

Split evenly between FBT and AFT, the patients were followed for a year of therapy and another year of follow-up. At the end of treatment, 42 percent of those enrolled in FBT showed full remission back to at least 95 percent of expected body weight, compared to only 23 percent of those enrolled in AFT. While that comparison fell just short of statistical significance, with a p-value of .055, Le Grange said that the higher standards used in the study spoke to the effectiveness of FBT.

“We used the higher yardstick for remission of 95 percent of body weight, which we felt was clinically more appropriate,” said Le Grange, a professor of psychiatry and behavioral neuroscience.

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Cancer successes are usually measured in months, not years. Large clinical trial on promising new treatments are celebrated when they show an average effect of a dozen weeks, and extension of life that can be measured in years is cause for rapture. So a new treatment that cuts down a high-risk cancer’s recurrence rate over a 2-year period by 20 percent is a major leap forward - even if the cancer is not among the most common types.

The cancer, in this case, is neuroblastoma, a tumor originating in nerve tissues outside the brain that predominantly strikes children under the age of 5. Though there are only 650 estimated new cases of neuroblastoma in the United States every year, that’s still enough for it to rank as the second most common solid tumor in children. While successful cures for low and intermediate-risk neuroblastoma cases have been found, roughly half of patients have a “high-risk” form of the disease that has only a 40 percent survival rate. That makes the new research, published today in the New England Journal of Medicine, the biggest advance in more than a decade for patients and families affected by the most deadly forms of the disease.

“Neuroblastoma is a rare pediatric cancer, but this is so, so, so, remarkable,” said Susan Cohn, professor of pediatrics at Comer Children’s Hospital and an author of the study. “To improve survival rates by 20 percent is fantastic.”

The treatment at the heart of the study is a form of immunotherapy, the drug strategy that seeks to recruit a patient’s native immune system to attack the tumor. An antibody against a protein expressed by tumor cells, called ch14.18, is the central prong of the three-drug therapy tested in the trial. Two other drugs, interleukin-2 and GM-CSF, are immune factors designed to help stimulate white blood cells to kill tumor cells. In the trial’s experimental group, this trio of drugs was added to the normal course of therapy for high-risk neuroblastoma, which includes surgery, chemotherapy, radiation, a transplant of the patient’s own stem cells to restore healthy blood cells, and retinoic acid.

Recruiting patients for the trial was a long and arduous process, Cohn said, due to concerns from patients’ families about trial randomization and side effects. Ten years of recruitment later, the study had enough power to be stopped — when analysis of the results showed an overwhelmingly positive effect of treatment, it was considered unethical to proceed. Patients in the control group were given the option of switching to the immunotherapy, and new patients were enrolled in a non-randomized trial to continue assessing long-term effects of the treatment.

Understanding the toxicity of the treatment is especially important, as the initial trial revealed a suite of side effects that accompanied the substantial benefits. Pain, reduced blood pressure, fluid in the lungs, and other adverse effects need to be closely watched by health professionals during the treatment, Cohn said.

“It’s not an easy therapy; there are lots of side effects and patients must be monitored carefully while they are receiving treatment in the hospital,” Cohn said. “If it hadn’t shown a clear advantage, we would no longer do it.”

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Dr. William Dale talks with a patient in his geriatrics clinic (photo by Bart Harris)

Creating a new research field doesn’t happen overnight. It requires bringing together like-minded researchers willing to push out into the unknown, funding agencies willing to be convinced that the new field is worth of grant dollars, and some semblance of an overall plan so that those efforts and dollars are put to optimal use. Soldering together a new field out of two existing fields can save some of the groundwork, but also creates its own set of obstacles, as representatives from each pre-existing discipline maneuver for common ground with their colleagues from across the fence.

The very young field of geriatric oncology, the study of cancer and cancer treatments in the elderly, has already jumped some of those hurdles. Most importantly, the field has a very good reason to exist, as cancer is primarily a disease of the elderly, and the U.S. population is growing increasingly older as baby boomers reach retirement age. Clinics focused on the care of elderly patients with cancer have sprung to life, including the SOCARE Clinic at the University of Chicago Medical Center. Yet there remains a void of knowledge about how cancer forms, grows, and can potentially be cured in older patients, due to clinical trials that enroll primarily younger subjects. Filling that void - and creating a field to do so - was the focus of a two-day conference last weekend at the Hilton O’Hare, where 50 members of the newly-formed Cancer & Aging Research Group discussed the fine details of how best to proceed.

Two numbers presented by NYU’s Daniel Gardner and echoed by several others demonstrated the need for geriatric oncology research: 61 percent of new cancer cases occur in people older than 65, but only 25 percent of patients on cancer clinical trials are from that age group. What’s more, the elderly that do make it into trials of new drugs and therapies are a special breed - “Olympic athletes” that meet strict enrollment requirements designed to pick research subjects that are largely free of co-morbid health conditions beyond their cancer. That leaves physicians in the dark about how to treat less healthy elderly cancer patients, with no evidence to guide their treatment decisions.

“For the vulnerable and frail adults, there’s so little data…it’s a really big population that’s coming to the clinic right now, where almost every patient I see I don’t have the right kind of evidence for,” said Supriya Mohile from the University of Rochester, who organized the conference with Arti Hurria from City of Hope Hospital in California and William Dale, section chief of geriatrics and palliative medicine at the University of Chicago.

One central question of the conference was whether to remedy that shortage by designing clinical trials specifically for older patients or by lobbying clinical researchers to include more elderly subjects in trials. Both solutions hinge upon improving recruitment rates for elderly patients, the burden of which often falls on the researchers themselves. In a talk titled “We Have Met the Enemy, and it is Us,” University of Chicago assistant professor Blase Polite showed data from several studies showing that patients older than 65 are typically half as likely to be offered an experimental cancer treatment. When elderly patients are offered the chance to enroll in a clinical trial, they are as likely - if not more so - as those under 65 to say Yes, he found.

The gap in enrolling elderly patients in clinical trial may stem from a larger problem of physician-patient communication, many presenters argued. Decisions about cancer treatment are certainly different for a 45-year-old vs. a 75-year-old, and a patient’s weighing of treatment side effects, quality of life, and the chance of a cure may change with age. But as Northwestern’s Linda Emanuel argued, physicians need to better understand that internal calculus for elderly patients facing the possibility of death.

“[There are] gratifications that are unique to those that are facing the end of life, through age or through cancer or through other terminal conditions,” Emanuel said. “What is that kind of wellbeing? I don’t think we know, we in the research field. We don’t have measures for it and we don’t have methods for it.”

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Covering medical research for the University of Chicago, one hears a lot about racial health disparities and the efforts to narrow those gaps. But some statistics still pack a punch, and Otis Webb Brawley’s talk at the University of Chicago last Thursday contained several left hooks. The five-year risk of death after diagnosis with breast cancer is almost twice as high for black women as for white women - but 30 years ago, the risk was nearly equal. An uninsured patient with stage 1 colon cancer is more likely to die from their disease than an insured patient with the more-dangerous stage 2 colon cancer. Obesity in children has risen five-fold since 1970, and obesity is expected to pass cancer as the #1 cause of cancer by the year 2030…if it hasn’t already.

In Brawley’s role as chief medical and scientific officer for the American Cancer Society, it’s his job to use these statistics to make clear arguments to scientists, physicians, politicians, and laypeople about what must be done to reduce cancer disparities. But Brawley’s talk for the Bowman Society Lecture Series (named for retired professor, and former teacher of Brawley at the Pritzker School of Medicine, James Bowman), was distinctly not about just throwing money at the problem. His central philosophy was “equal treatment yields equal outcomes among equal patients” - but sometimes, deciding what that equal treatment should be is the hard part.

Brawley took care to set his talk in the context of spiraling health care costs in the United States, showing the now-familiar graph plotting our highest-in-the-world health care spending against the country’s mediocre life expectancy. Racial disparities could explain part of those poor returns on US health care spending, but Brawley put the focus on “faith-based medicine” - not health care based on religion, but care (and associated spending) based on assumptions about what works rather than hard evidence. As an example, Brawley cited the practice of chest X-ray screening, considered by physicians in the 1960’s to be a necessary routine procedure for the detection of cardiopulmonary disease. But clinical trials found that these screens caused more harm than good, through increased rates of lung cancer and over-diagnosis.

“We did all those things because we thought we were doing the right thing, but we didn’t do rigorous assessment before we started doing them,” Brawley said. “So I ask the question: are we willing to be scientific and accept scientific realities? There are things that we do that add to the incredible cost of health care, but make no difference in outcome.”

That tough talk should apply equally to the problem of reducing health disparities in minority populations, Brawley emphasized. While some pursue the genetic risk factors that may explain disparate rates of disease in minorities, Brawley argued that socioeconomic factors were a much bigger target for intervention. A 1998 study that compared the breast cancer mortality gap in the general population versus women in the U.S. military medical system (who receive free health insurance and easier access to hospital care) found that the gap was still there, but almost two-thirds smaller. The other third could be genetics, Brawley conceded, but the more significant - and, in his view, easier to fix - factors were social and economic.

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Just twenty years ago, there were no therapies available for the management of multiple sclerosis. Physicians could give patients drugs to try and blunt the damage caused by the disease’s intermittent attacks on the central nervous system, but no therapies had been proven effective at preventing those attacks. That changed in the mid-90’s, when successful studies and clinical trials led to the approval of interferon therapies, immune system modulators that block the autoimmune response responsible for MS attacks.

Interferon therapies have since multiplied, and other MS treatments have come to market. But each of these approaches have side effects, must be delivered by injections, and don’t work in every patient. Today, the FDA approved a sixth MS therapy, called fingolimod - the first protection against MS attacks available as a pill. Experts welcomed the decision, saying it would give neurologists a valuable new weapon in the fight against multiple sclerosis.

“This is the first pill for multiple sclerosis,” said Anthony Reder, MD, professor of neurology at the University of Chicago Medical Center. “We have six drugs right now, and they all involve injections. So the convenience alone of a pill is a major change in how we treat MS. It also expands the drugs available to treat MS, and may get some people who can’t take the other medicines. It will be used to replace drugs that are failing and possibly for new starts in some people.”

Fingolimod, code-named FTY-720 in trials and soon to be released by drug company Novartis as Gilenya, took a strange route to the clinic. The drug is based on a type of fungus, originally discovered in the intestines of wasps by Japanese researchers. Observing that the fungus secreted a chemical with the natural ability to suppress immune responses, scientists refined the chemical into a drug intended for use in people receiving transplanted organs. The eventual clinical trials for that use failed, but a secondary use presented itself: neutralizing the immune system attacks in multiple sclerosis patients.

This time around, the clinical data was much more successful. The results of two large Phase III clinical trials published in the New England Journal of Medicine in February showed exciting effects - a roughly 50 percent decrease in attacks in patients treated with fingolimod relative to patients receiving placebo or interferon therapy. MRI images also showed that fingolimod-treated subjects had fewer brain lesions, signs of progressive, permanent damage caused by MS attacks. Some side effects were observed, such as a transient decrease in heart rate after the first dose and a slight uptick in the number of infections, and experts said those will need to be monitored as the drug reaches a wide population.

“As always with these drugs, the people in study were a restricted group of patients with no cardiac disease, no diabetes, no pulmonary abnormalities,” Reder said. “When we go out into the real world, we have to be more conscious of potential side effects and interactions with other conditions.”

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There are many today who argue that the future of medicine is in data mining. Massive computational efforts are underway to collect mountains of data from multiple sources - genomic sequencing, clinical trial results, laboratory experiments - and put them to work in the unbiased, abstract mind of the high-throughput supercomputer. The biological world is too complicated in many places for us to make significant therapeutic advances, the argument goes, so only a computer can sniff out the intricate patterns that can be exploited to fight disease.

But eventually, this new approach to science will come up against an old obstacle: the best ideas, whether born in a computer or on a laboratory chalkboard, don’t always work. Coming up with a hypothesis - intervention x will affect disease y - is only the first part of the scientific method. Testing that hypothesis is where the real advances are made, and where many new drugs and therapies have crashed upon the shores of reality. In a new article this week in Science Translational Medicine, a University of Chicago surgeon argues that computers also have a role to play in that second part of the equation.

Gary An, a brand new member of the surgical faculty at the University of Chicago Medical Center, observed the “translational dilemma” firsthand early in his career. Working in the critical care unit at Cook County Hospital, An saw patient after patient succumb to sepsis, an overwhelming, stubborn infection of the body that leads to organ failure and often death. An enormous body of research has described the biological steps that underlie sepsis, but almost every intervention proposed by that research has failed in clinical trials.

“None of those things tried at that time worked; in fact, some of them were even detrimental,” An said. “The critical care literature were filled with editorials - ‘What are we doing wrong? What’s the problem?’”

Those failures led An to the study of complexity, systems where the overall behavior is not explained simply by the underlying rules. An reasoned that the only way to properly study such a system is to generate computer models capable of testing hypotheses, not just creating them. With computer modeling software that was relatively easy to learn - “designed to teach elementary school students about bird and traffic,” he said - An created an in silico model of sepsis.

The model drew upon published research to create a biological network of immune system factors that simulated a real patient experiencing sepsis. Then he re-ran the strategies tested in the clinical trials - and found results (published in 2004) that could have saved drug companies and researchers a lot of time and money.

“As it turns out, none of them worked, and some of them actually hurt simulated patients, which is what the trials showed,” An said. “The result of the simulated trial itself is not novel, we knew that was how it would happen. But if you had these means of testing the plausibility of the interventions that you had in mind [before the trial], it would have caused you to think about whether this is actually a good idea before you spend millions on clinical trials.”

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Personalized Medicine: The Brake vs. The Accelerator

A recurring theme on the blog - and presumably on every other medicine and science blog - has been the push toward personalized medicine, the utopian future where every patient receives individualized care for a disease or even the genetic risk of disease. But the road to that future world of health care has been slower than some experts anticipated, with disappointing clinical trials, scientific setbacks and regulatory hurdles all acting as speed bumps. Those obstacles are partially why National Institutes of Health director Francis Collins was dinged this week in a New York Times article for promising “a complete transformation in therapeutic medicine” within a decade or two of the Human Genome Project’s completion…ten years ago.

So it was interesting to see Collins’ revised opinion on the timeline for personalized medicine this week in the New England Journal of Medicine, in an editorial co-written with FDA Commissioner Margaret Hamburg. It’s a strange partnership in some ways: the country’s top scientist and the country’s top regulator. The editorial reads accordingly, with a first half marked by the go-go optimism of Collins followed by the “woah, let’s slow down” realism of Hamburg.

Still, there are some interesting initiatives within. Collins gives the glass-half-full version of the New York Times’ Human Genome Project assessment, stating that hundreds of disease-related gene variants have been characterized and are now promising drug targets. The issue, Collins claims is the lack of financial incentives for companies to pursue those targets, something he hopes to fix by allowing the NIH to step in and do the preclinical “Valley of Death” work that scares off pharmaceutical companies. Collins also promises an expanded effort to establish tissue banks and genetic databases from clinical trials and epidemiological studies such as the Framingham Heart Study, to enable better research into biomarkers that predict disease or response to treatment.

On the flipside, Hamburg argues that extreme caution should be employed in approving tests for those very biomarkers. Her argument - that most current tests are inaccurate or misleading - is backed up by the FDA’s recent move to more aggressively regulate test marketed for at-home use. While the editorial offers a table of three tests approved to predict a patient’s response to a cancer drug such as Gleevec or cetuximab, Hamburg writes that some 2,000 genetic tests are currently used by clinical laboratories - some FDA-approved, some not. The editorial promises a genetic testing registry that will offer consumers and physicians information about the tests, but promises that the agency will keep a close eye on tests that “are broadly marketed to laboratories or the public.”

If that sounds all a bit good cop/bad cop, it’s true. The key will be in the balance between the forces pushing personalized medicine forward and those entrusted with testing its validity. As Collins and Hamburg put it, “When the federal government created the national highway system, it did not tell people where to drive - it built the roads and set the standards for safety…We are now building a national highway system for personalized medicine.”

More World Cup Science

When I wrote my World Cup science piece last week, I didn’t realize that several scientists were holding back their timely soccer-science articles until the tournament was in full swing. But sure enough, a flood of new research has crossed the wires in the past week, about everything from the controversial vuvuzela horns to the age-old debate of “soccer” vs. “football.”

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Most scientific conferences contain two very different approaches to storytelling. On the exhibit floor, pharmaceutical companies, laboratory suppliers, publishers and chambers of commerce compete for attendee’s attention with ever more grandiose booths that resemble small palaces. But in the many, many rooms surrounding that circus, scientific data is presented (usually) in decidedly unflashy fashion, thanks to the understated personalities of most scientists and a sense of research presentation propriety. 

The American Society of Clinical Oncology meeting illustrated that divide more vividly than any other scientific conference I’ve attended. Just last month, I was impressed by the exhibit booth architecture display at the BIO meeting, but the exhibitor showcase at ASCO made other conferences’ huts look like a miniature golf course. With Jumbotron-sized video monitors, 3D animations, futuristic chairs, and more sales reps per square foot than anywhere else in the world, it’s an overstimulating experience to walk through.

But the research presentations of ASCO are the polar opposite - quick-fire 15-minute “just the data” talks light on drama even as exciting new treatments are described. The structure for presenting clinical trial results is apparently very codified for cancer researcher: provide rationale for trial, describe study design, show effect of treatment (or lack thereof), compare side effects to other treatments, suggest future directions. Context for the data is later provided by a discussant, who is at more liberty to deliver a judgement on whether the findings have immediate clinical relevance. Whether that’s down to ethics or merely tradition, it’s a much more formal experience than other conferences I’ve seen.

The overwhelming size of the conference makes it hard to deliver a 30,000-foot overview of the proceedings; one must merely pick a particular cancer track and hope for the best. On Monday, following the University of Chicago trail led me to a series of presentations on head and neck cancer, a particular specialty of the Medical Center and our current CEO, Everett Vokes. Like all cancer types, the head and neck variety can be broken down into several sub-types, including thyroid cancer, which can be further broken down into its own sub-types. One disease on the smaller end of this Russian nesting doll hierarchy is medullary thyroid cancer (MTC), diagnosed in only 1,400 Americans a year but essentially untreatable.

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In 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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The Mars 500 "spaceship." (taken from http://mars500.imbp.ru)

One of my favorite rides at the Magic Kingdom in Disneyworld was the now-defunct Mission to Mars, a perfect representative of the space age optimism on display in Tomorrowland. For those of you too young to experience it firsthand, it was charmingly simple: a circular theater with video screens above (showing Mars getting bigger) and below (where Earth got smaller) as audio cues played and the seats vibrated a little bit. As a simulation of real space travel, it was hardly SpaceCamp - or even Space Mountain - but you took what you could get in the ’80s.

Nowadays, when an actual mission to Mars seems slightly less improbable, Russian scientists are about to begin a slightly more accurate simulation of what such a journey might entail. Only in this case, the experience will take a little longer than the Disneyworld ride - it’s a 520-day isolation experiment called Mars 500 to study the psychological effects on astronauts kept in a confined space for that lengthy time. Yesterday, the “astronauts” entered their capsule, which looks kind of like a human-sized hamster tube system and includes kitchens, a gym, an experimental greenhouse and even a “simulator of the Martian surface.” The questions that the experiment hopes to answer - such as the all-important “how do you not get bored?” and “how do you avoid fights and sexual harassment?”- are addressed by New Scientist and Discover and you can watch video of the “launch” at the New York Times.

Labapalooza Kicks Off

Summertime means music festivals - overdosing on bands, getting sunburned and dehydrated and eating expensive food. It’s great. But before the street fairs and tent cities get into the full swing, you can enjoy a different kind of festival from your own couch this weekend. The World Science Festival, which has been held each year in New York City since 2008, is running a number of live webcasts from the event through Sunday night. It actually started rolling yesterday, with the announcement of the Kavli Prize winners and a panel on black holes and holographic worlds (hosted by famous science geek Alan Alda), both of which are archived and viewable any time. Tonight features some intense math, while tomorrow they will broadcast on panel on animal intelligence and a nighttime discussion of hyperspace, which I only know about from comics. It looks like a cool event, accessible to both casual and serious sci-curious.

Elsewhere...

The ginormous American Society of Clinical Oncology meeting kicks off today in Chicago, with five solid days of presentations about the latest in cancer research and treatments. I’ll be there for a couple days of the conference, and will have some blog coverage next week. In the meantime, if you dare take a glimpse of the complicated world of science journalism and publicity, Ron Winslow at the Wall Street Journal Health Blog has a very funny post about some embargo shenanigans in the run-up to the meeting.

I’m sad to report that Philip S. Ulinski, a neuroscientist, professor emeritus and former department chair who spent 35 years at the University of Chicago, passed away last week. Here’s the obituary I prepared for the University. Dr. Ulinski leaves behind a remarkable legacy: the Committee on Computational Neuroscience, one of the first programs to offer a PhD in the study of the brain using the latest computational tools. 

Since I wrote about the Nature Neuroscience acupuncture study on Tuesday, there has been some more commentary from around the web - most of it unfavorable to the study’s authors and the media coverage of their finding. Here’s the blog Respectful Insolence (who does a great job monitoring and debunking “alternative therapies” built on shaky science) pointing out the true interesting result of the paper, and DC’s Improbable Science dissecting the media coverage and press release.

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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