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Cardiovascular Medicine, Chronic Disease, In the News, Research, Science, Stanford News

How best to treat dialysis patients with heart disease

How best to treat dialysis patients with heart disease

523392_4923732760_zKidney failure patients on dialysis often have other chronic diseases – heart disease topping the list. They’re prescribed an average of 12 pills a day by physicians, according to Stanford nephrologist Tara Chang, MD, and they spend three-to-four hours at a treatment center three times a week connected to an artificial kidney machine.

For Chang, this makes it all the more important that any medication she prescribes for a patient on dialysis is both essential and effective.

The problem is, particularly in the case of treating kidney patients with heart disease, evidence-based treatment guidelines just aren’t available. Kidney doctors are left making best guesses based on guidelines written for the general population.

“Our patients might be different from patients not on dialysis,” said Chang. “Dialysis patients have a lot of heart disease, yet rarely does a cardiology study enroll patients on dialysis, so we just don’t know.”

This was part of the motivation behind Chang’s most recent study examining the use of anti-platelet drugs such as clopidogrel, one of the most commonly prescribed drugs for kidney patients. The researchers looked at the use of anti-platelet medications such as clopidogrel as treatment following stenting procedures to unclog arteries in the heart in 8,458 dialysis patients between 2007 and 2010. The data suggests that longer-duration of drug use may be of benefit to patients on dialysis who get drug-eluding stents but not those who get bare metal stents. Chang told me:

We found that for those who got drug-eluting stents who took the drug for 12 months compared to those who had stopped the drug at some earlier time point, there was a non-statistically significant trend towards lower risks of death and heart attacks. So for this group, following the same guidelines as for the general population may be appropriate. However, we found no indication of benefit with longer duration of anti-platelet drug use for patients on dialysis who got bare metal stents.

About half of the 400,000 patients in the U.S. on dialysis also have coronary artery disease, as referenced in the study. The number of those getting stents inserted to unclog arteries also has increased 50 percent in the past decade, the study states. The results of the study, while not definitive as to exactly how long doctors should prescribe the drug, does stress the need for more clinical research on patients with kidney failure to provide guidance on treatment strategies for heart disease.

“Because our study was not a randomized trial,” said Chang, “we tried to be very measured in how we interpreted the results. What it does point to is the fact that we can’t assume that what works in non-dialysis patients works in dialysis patients. Hopefully our study will help convince researchers to include our dialysis patients in their studies.”

The paper was published this week in the Journal of the American Heart Association.

Previously: Keeping kidney failure patients out of the hospitalStudy shows higher rates of untreated kidney disease among older adults and Study shows daily dialysis may boost patients’ heart function, physical health.
Photo by newslighter

Ebola, In the News, Myths, Science

The slippery slope toward “a dangerous dependence on facts”

The slippery slope toward "a dangerous dependence on facts"

220px-Sputnik_asmThe ever-funny Andy Borowitz has written in The New Yorker about a previously unreported challenge in the fight against Ebola: It might make Americans believe in science. He writes:

In interviews conducted across the nation, leading anti-science activists expressed their concern that the American people, wracked with anxiety over the possible spread of the virus, might desperately look to science to save the day.

“It’s a very human reaction,” said Harland Dorrinson, a prominent anti-science activist from Springfield, Missouri. “If you put them under enough stress, perfectly rational people will panic and start believing in science.”

For someone who left science to become a writer specifically to help explain science to the public, this piece is both funny and also so very not funny at the same time. Almost 20 years after I put down my pipette, Americans are, if anything, less willing to let science guide their health, energy, or environmental decisions than they were back when I started – thus the humor in Borowitz’ piece.

All of this makes me wonder if I could have spared myself several decades of worrying about clever analogies, agonizing about transitions, and racing the clock to make deadlines and done something less stressful with my life. Something fulfilling. Something where at the end of the day, my work would help people live happier, healthier lives rather than producing something people will ignore if it doesn’t fit their ideology.

Matthew Nisbet and Dietram Scheufele have written a number of articles about science communication and its effects on public perception of science. In the American Journal of Botony they write, “Often when the relationship between science and society breaks down, science illiteracy is typically blamed, the absence of quality science coverage is bemoaned, and there is a call put out for ‘more Carl Sagans.’”

In a nutshell, that sums up my career switch. I bemoaned the absence of quality science coverage and fully intended to fill that gap.

Then, they go on to shatter my reasons for writing by pointing out that at a period of time when the public’s regard for science was at it’s highest – soon after the Sputnik launch – science literacy was abysmal. In one survey at the time, just 12 percent of people understood the scientific method, yet 90 percent of people believed that science was making their lives better.

What that survey suggests is that even a scientific challenge like Ebola is unlikely to push Americans to be better educated about science. But perhaps with the perfect transition, or really outstanding analogy, those same scientifically illiterate Americans can be convinced that science is making life better and – I’m really dreaming here -should be funded?

If yes, maybe Borowitz’ fictional anti-science advocate will be proved right, and we will head down that slippery slope “in which a belief in science leads to a belief in math, which in turn fosters a dangerous dependence on facts.” One can hope!

Previously: Scientist: Just because someone’s on TV doesn’t mean they’re an expert

Dermatology, Research, Science, Stanford News, Stem Cells

The politics of destruction: Short-lived RNA helps stem cells turn on a dime

The politics of destruction: Short-lived RNA helps stem cells turn on a dime

Many stem cells live a life of monotony, biding their time until they’re needed to repair tissue damage or propel the growth of a developing embryo. But when the time is right, they must spring into action without hesitation. Like Clark Kent in a phone booth, they fling aside their former identity to become the needed skin, muscle, bone or other cell types.

Now researchers at Stanford, Harvard and the University of California-Los Angeles have learned that embryonic stem cells in mice and humans chemically tag RNA messages encoding key stem-cell genes. The tags tell the cell not to let the messages linger, but to degrade them quickly. Getting rid of those messages allows the cells to respond more nimbly to their new marching orders. As dermatology professor Howard Chang, MD, PhD, explained to me in an email:

Until now, we’ve not fully understood how RNA messages within the cell dissipate. In many cases, it was thought to be somewhat random. This research shows that embryonic stem cells actively tag RNA messages that they may later need to forget. In the absence of this mechanism, the stem cells are never able to forget they are stem cells. They are stuck and cannot become brain, heart or gut, for example.

Chang, who is a Howard Hughes Medical Institute investigator and a member of the Stanford Cancer Institute, is a co-senior author of a paper describing the research, which was published today in Cell Stem Cell. He shares senior authorship with Yi Xing, PhD, an associate professor of microbiology, immunology and molecular genetics at UCLA, and Cosmas Giallourakis, MD, an assistant professor of medicine at Harvard. Lead authorship is shared by postdoctoral scholars Pedro Batista, PhD, of Stanford, and Jinkai Wang, PhD, of UCLA; and by senior research fellow Benoit Molinie, PhD, of Harvard.

Messenger RNAs are used to convey information from the genes in a cell’s nucleus to protein-making factories in the cytoplasm. They carry the instructions necessary to assemble the hundreds of thousands of individual proteins that do the work of the cell. When, where and how long each protein is made is a carefully orchestrated process that controls the fate of the cell. For example, embryonic stem cells, which can become any cell in the body, maintain their “stemness” through the ongoing production of proteins known to confer pluripotency, a term used to describe how these cells can become any cell in the body.

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Cancer, Clinical Trials, Research, Science, Stanford News, Stem Cells

Drug may prevent bladder cancer progression, say Stanford researchers

Drug may prevent bladder cancer progression, say Stanford researchers

Bladder cancer is an insidious foe. About 70 percent of the time the condition is diagnosed while still confined to the bladder lining (in these cases, it’s known as a “carcinoma in situ,” or CIS). However, a subset of these localized cancers will go on to invade tissue surrounding the bladder and become much more deadly.

Now, developmental biologist Philip Beachy, PhD, a Howard Hughes Medical Institute investigator, and his colleagues have found that low doses of a drug called FK506 currently used to prevent the rejection of transplanted organs can prevent the progression of CIS into invasive bladder cancer in mice. Beachy collaborated with collaborated with urologist Joseph Liao, MD, and pulmonary specialist Edda Spiekerkoetter, MD, to conduct the research, which was published today in Cancer Cell. As Beachy explains in our release:

This could be a boon to the management of bladder cancer patients. Bladder cancer is the most expensive cancer to treat per patient because most patients require continual monitoring. The effective prevention of progression to invasive carcinoma would be a major advance in the treatment of this disease.

Beachy and Liao are members of the Stanford Cancer Institute. Together they’re hoping to initiate clinical trials of FK506 in people with CIS to learn whether the drug can also prevent progression to invasive cancer in humans.

The findings of the current study build upon previous research into the disease in Beachy’s laboratory and a long-time interest by Beachy in a molecular signaling pathway governed by a protein called sonic hedgehog. Beachy identified the first hedgehog protein in 1992; the protein (and the hedgehog pathway) have since been shown to play a vital role in embryonic developments and many types of cancers. Sonic hedgehog, Beachy has found, is produced by specialized stem cells in the bladder as a way to communicate with neighboring cells. They learned it’s required for the formation of CIS, but that it must also be lost in order for the cancer cells to invade other tissues. As Beachy explained in our release:

This was a very provocative finding. It was clear that these [sonic-hedgehog-expressing] bladder stem cells were the source of the intermediate cancers, or carcinomas in situ, that remain confined to the bladder lining. However, it was equally clear that sonic hedgehog expression must then be lost in order for those cancer cells to be able to invade surrounding tissue. We wondered whether the loss of this expression leads to increased tumor cell growth.

The researchers found that sonic hedgehog expression works in a loop with another class of proteins called BMPs. (You can read more about this in our release.) FK506 works by activating the BMP portion of the pathway in the absence of sonic hedgehog. Ten out of ten mice with CIS who received a low dose of the drug (low enough not to cause immunosuppression) were protected from developing invasive bladder cancer after five months of exposure to the carcinogen. In contrast, seven of nine mice receiving a placebo did develop the invasive form of the disease within the same time period.

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Science, Stanford News, Videos

The “simply amazing” work of Nobel Prize winner W.E. Moerner

The "simply amazing" work of Nobel Prize winner W.E. Moerner

Yesterday Stanford chemistry professor W.E. Moerner, PhD, was named a co-winner of the 2014 Nobel Prize in Chemistry for his work in super-resolution microscopy. In the video above, his colleagues – including Stanford Medicine’s own Lucy Shapiro, PhD, – share their thoughts on his work and the win. “The ability to now look at… mechanisms in a living cell is simply amazing,” Shapiro concluded.

Previously: Breaking the light barrier in medical microscopy: More on today’s Nobel-winning work and For third year in row, a Stanford faculty member wins the Nobel Prize in Chemistry

Imaging, Research, Science, Stanford News, Videos

Breaking the light barrier in medical microscopy: More on today’s Nobel-winning work

Breaking the light barrier in medical microscopy: More on today's Nobel-winning work

Earlier today, Stanford University’s W.E. Moerner, PhD, was one of three scientists to be awarded the Nobel Prize in Chemistry for work in super-resolution microscopy. Before this technology, the only way to look at structures inside cells was with electron microscopy. But that requires researchers to kill the tissue in order to prepare it for the microscope. Essentially, the objects being examined were frozen in place; scientists could make out cellular structures but couldn’t watch them in action.

Microscopes that use refracted light, or optical microscopes, can be used to observe living cells, but for decades, they were limited from going below 220 nanometers, a hard limit imposed by the wavelength of light. Eric Betzig, PhD, of Howard Hughes Medical Institute, and Stefan W. Hell, PhD, of the Max Planck Institute for Biophysical Chemistry in Germany shared the prize with Moerner for work that helped break that barrier. Now, researchers can peek inside cells as they are going about their business and observe real-time changes as they happen.

This morning, Moerner spoke to Stanford’s news office via Skype from Brazil about his work and how other researchers, including Lucy Shapiro, PhD, and Matt Scott, PhD, of Stanford’s School of Medicine are applying the new methods to medical research (see above video). Shapiro, a 10-year collaborator of Moerner’s, is examining structures inside bacteria and Scott is looking at subcellular signalling structures. (Shapiro provides comment on her work in a Stanford press release.)

“Because of this revolutionary work, scientists can now visualize the pathways of individual molecules inside living cells,” Francis Collins, MD, PhD, director of the National Institutes of Health, which funds some of Moerner’s work, said in a statement. “Researchers can see how molecules create synapses between nerve cells in the brain, and they can track proteins involved in Parkinson’s, Alzheimer’s and Huntington’s diseases.”

Below is a clip of Moerner describing what those studying Huntington’s disease have learned using the prize-winning microscopy technology.

Previously: For third year in row, a Stanford faculty member wins the Nobel Prize in Chemistry
Videos courtesy of Stanford University Communications

Science, Stanford News

For third year in row, a Stanford faculty member wins the Nobel Prize in Chemistry

For third year in row, a Stanford faculty member wins the Nobel Prize in Chemistry

Moerner

Stanford chemistry professor W.E. Moerner, PhD, has been named a co-winner of the 2014 Nobel Prize in Chemistry. An announcement was made earlier this morning by the Royal Swedish Academy of Sciences, which said the award was for “having bypassed a presumed scientific limitation stipulating that an optical microscope can never yield a resolution better than 0.2 micrometers.”

This is the third year in a row that a Stanford faculty member has received the chemistry award: Michael Levitt, PhD, and Brian Kobilka, MD, both from the medical school, won the prize in 2013 and 2012, respectively.

You can get updates on this news by following the hashtag #StanfordNobel.

Congratulations, Professor Moerner!

Previously: Say Cheese: A photo shoot with Stanford Medicine’s seven Nobel laureates, Stanford winners Michael Levitt and Thomas Südhof celebrate Nobel Week, Stanford’s Michael Levitt wins 2013 Nobel Prize in Chemistry, Stanford’s Thomas Südhof wins 2013 Nobel Prize in Medicine and Stanford’s Brian Kobilka wins 2012 Nobel Prize in Chemistry
Photo L.A. Cicero/Stanford News Service

Medical Education, Medicine and Society, Neuroscience, Science, Stanford News

Studying science at Stanford is a dream come true for one California man

Studying science at Stanford is a dream come true for one California man

new grad students

Tawaun Lucas grew up in Compton, East LA, a city with a reputation – whether deserved or not – for producing gangsters, not neuroscientists. It’s a reputation Lucas just ignored.

A high-school athlete who dreamed of playing  in the NFL or going to the Olympics, the 22-year-old instead joined this year’s entering class of neuroscience graduate students at Stanford with a new set of aspirations.

Dreams change, Lucas explained me when I interviewed him for a story I wrote about the 135 new bioscience graduate students starting the fall semester at Stanford. As I describe in the story:

Lucas only changed his aspirations from sports to science after being sidelined by injuries his sophomore year at California State University-Northridge, where he was on a scholarship as a track athlete. But starting Stanford’s neurosciences PhD program is a dream come true, he said. “Stanford was always my first choice,” he said. “I applied to 12 schools.” When he got the acceptance call from Stanford, he said he nearly dropped the phone. “I almost teared up and cried,” he said. “It was surreal. I can’t even describe the experience.”

Lucas’s mother worked as a bus driver for the Long Beach school district. His dad was a maintenance worker. No one in his family went to college, and he wasn’t a particularly good student in high school, so the path to studying neuroscience at Stanford was an unexpected one. But programs for underrepresented minorities in the sciences helped him along the way, as did his own fascination with human behavior and the study of the brain:

His interest in science didn’t develop until his undergraduate years. He was living at home at the time with his parents, working as a bank teller while attending Cal State Northridge.  He began to turn his energies to academics when athletics was no longer an option. “Once I figured out what I wanted to do, I became focused,” he said. He chose to study psychology because the environment he grew up in had sparked his curiosity about human behavior. “I grew up in an urban area around some pretty crazy people who made some pretty weird decisions,” he said. “I began to wonder why do people, say, raised in Compton or Watts, for example, make different choices than someone raised in, say, Manhattan Beach? Is it socioeconomic? Psychological? Is there a genetic element?

Anthony Ricci, PhD, a professor of otolaryngology and member of the Stanford Neurosciences Institute, who played a role in encouraging Lucas to apply to Stanford and is part of an institution-wide effort to encourage diversity in the sciences, emphasized just how important diversity is to future advances in science:

“A person’s background is really important to how they think about a problem,” Ricci said. “If everyone were white, middle-class, Harvard-trained, they might think too much alike. Science needs people who think differently.”

Previously: First-year science graduate students enter brave new world and No imposters here: Stanford grad students reassured as they begin school
Photo by Norbert von der Groeben

Genetics, In the News, Research, Science

Zebrafish: A must-have for biomedical labs

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Rats, mice and fruit flies be warned: The hippest lab critter around is a striped, little fish from South Asia called the zebrafish.

The fishies’ popularity is skyrocketing, as Susannah Locke recently wrote for Vox:

Zebrafish breed quickly, scientists can manipulate their genes easily, and the fish actually share a surprising number of similarities with humans.

As a result, researchers can study zebrafish to better understand how things like metabolism, birth defects, and even cancer work — and the results are often applicable to humans. So, for instance, it’s relatively quick and easy to test certain drugs on zebrafish. If those experiments yield promising results, the scientists can then do more targeted experiments with rodents. And then maybe, finally, with people.

Zebrafish have some unique characteristics that can be useful too: Zebrafish can regenerate heart, retina, spinal cord and fin tissue. Scientists are probing this ability to improve healing and potentially even cultivate new tissues. Their embryos are also transparent, allowing scientists to study organ development in real-time.

Scientists have grown quite masterful at manipulating their genes. As Locke writes: “Over the past five years, the cost of modifying a single gene in a zebrafish has dropped from $10,000 down to about $100.” That’s part of the reason why more than 2,000 biomedical papers are written each year using the fish.

Joseph Schech, DVM, knows these animals well:

“They’re very hardy. They’re very forgiving,” says Schech, a laboratory veterinarian in charge of roughly 200,000 zebrafish (and several other species) at the National Institutes of Health. ”They are very adaptable in the wild. They live in clear mountain streams. They live in muddy rice paddies. They can do a wide range of temperature if they have time to adapt to it.”

He’s in charge of keeping the creatures healthy in a NIH zebrafish facility that’s currently used by some 21 different laboratories. It’s one of the largest zebrafish facilities in the world — a single 78–80°F room that holds about 10,000 small tanks with a total of roughly 200,000 fish. The zebrafish eat a diet of brine shrimp grown in a nearby room and can be trained to spawn on cue.

Numerous Stanford labs use zebrafish for all sorts of research: William Talbot, PhD, is examining the development of the vertebrate nervous system; Gill Bejerano, PhD, is probing its genetics; and James Chen, PhD, is looking at its ability to regenerate tissue, to name just a few.

Previously: Researchers capture detailed three-dimensional images of cardiac dynamics in zebrafish, The importance of the zebrafish in biomedicineCellular-level video of brain activity in a zebrafish and A very small fish with very big potential
Image by Bob Jenkins

Big data, Research, Science, Stanford News, Technology

Gamers: The new face of scientific research?

Gamers: The new face of scientific research?

gamerMuch has been written about the lack of reproducibility of results claimed by even well-meaning, upright scientists. Notably, a 2005 PLoS paper (by Stanford health-research policy expert John Ioannidis, MD, DSci) with the unforgettable title, “Why Most Published Research Findings Are False”, has been viewed more than a million times.

Who knew that relief could come in the form of hordes of science-naive gamers?

The notion of crowdsourcing difficult scientific problems is no longer breaking news. A few years ago I wrote a story about Stanford biochemist Rhiju Das, PhD, who was using an interactive online videogame called EteRNA he’d co-invented to come up with potential structures for RNA molecules.

RNA is a wiggly wonder. Chemically similar to DNA but infinitely more flexible and mobile, RNA can and does perform all kinds of critical tasks within every living cell. Scientists are discovering more about RNA’s once-undreamed of versatility on a steady basis. RNA may even have been around before DNA was, making it the precursor that gave rise to all life on our planet.

But EteRNA gamers need know nothing about RNA, or even about biology. They just need to be puzzle-solvers willing to learn and follow the rules of the game. Competing players’ suggested structures for a given variety of RNA molecule are actually tested in Das’s laboratory to see whether they, indeed, stably fold into the predicted structures.

More than 150,000 gamers have registered on EteRNA; at any given moment, there are about 40 active players plugging away at a solution. Several broadly similar games devoted to pursuing biological insights through crowdsourcing  are also up and running.

Das and EteRNA’s co-inventor, Adrien Treuille, PhD, (now at Carnegie Mellon University) think the gaming approach to biology offers some distinct – and to many scientists, perhaps unexpected – advantages over the more-traditional scientific method by which scientists solve problems: form a hypothesis, rigorously test it in your lab under controlled conditions, and keep it all to yourself until you at last submit your methods, data and conclusions to a journal for peer review and, if all goes well, publication.

In this “think piece” article in Trends in Biochemical Sciences,  Treuille and Das write:

Despite an elaborate peer review system, issues such as data manipulation, lack of reproducibility, lack of predictive tests, and cherry-picking among numerous unreported data occur frequently and, in some fields, may be pervasive.

There is an inherent hint of bias, the authors note, in the notion of fitting one’s data to a hypothesis: It’s always tempting to report or emphasize only data that fits your hypothesis or, conversely, look at the data you’ve produced and then tailor the “hypothesis” accordingly (thereby presenting a “proof” that may never be independently and rigorously tested experimentally).

Das and Treuille argue that the “open laboratory” nature of online games prevents data manipulation, allows rapid tests of reproducibility, and “requires rigorous adherence to the scientific method: a nontrivial prediction or hypothesis must precede each experiment.”

Das says, “It only recently hit us that EteRNA, despite being a game, is an unusually rigorous way to do science.”

Previously: John Ioaniddis discusses the popularity of his paper examining the reliability of scientific researchHow a community of online gamers is changing basic biomedical researchParamecia PacMan: Researchers create video games using living organisms and Mob science: Video game, EteRNA, lets amateurs advance RNA research
Photo by Radly J Phoenix

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