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Scope is taking a Thanksgiving break

Scope is taking a Thanksgiving break


We’re signing off for the holiday, and we’ll resume our normal publishing schedule on Monday, Nov. 30. Happy Thanksgiving!

Photo by Cat

Cardiovascular Medicine, Medical Education, Patient Care, Stanford Medicine Unplugged

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Pathology vs. patients: Balancing morbid fascination with heart-felt care

Stanford Medicine Unplugged (formerly SMS Unplugged) is a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week during the academic year; the entire blog series can be found in the Stanford Medicine Unplugged category.

3690107655_eef7c24702_zI recently saw a patient who, against all odds, survived an aortic dissection. Miraculously, he was alive after the wall of his aorta — the largest and most important vessel in the body — began to rip apart. Aortic dissections are so violent and agonizing that a large portion of these patients don’t survive. Yet somehow, my patient was still able to sit upright in his chair and recount his story to me just a day after his surgery, a testimony to how far medicine has advanced and to how lucky he was.

I admit that I was more fascinated by his cardiovascular travails than I was concerned by his suffering and the long road of recovery awaiting him. After all, it was only a few months prior that we learned the pathophysiology of aortic dissections. And now in front of me was a real life case study accompanied by authentic lab values, imaging, and physical exam findings, all of which were free for me to probe.

Had I encountered him prior to medical school, I would have spent more time to express words of support and sympathy — he’s a survivor and he needed any and all means of encouragement to return to some semblance of normalcy.

Once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

But medical school, for better or worse, changes your perception of patients and their plights. Despite all the efforts in the curriculum to teach us to view the patient as a whole, the endless nights and sacrificed weekends of burying ourselves in textbooks and scrambled jargon eventually dehumanizes patients and forces the spotlight on the pathology.

Call it insensitivity or callousness, but this morbid fascination with human illness is one of the paradoxes in medicine — that we must sympathize with the patient as well as with the disease that is harming him and may eventually kill him.

And for better or worse, becoming a competent doctor requires some modicum of this perverse curiosity, a veritable double-edged sword. Anyone who lacks it would simply not be able to survive four years of college dedicated mostly to studying basic biology, another four years of medical school to studying clinical presentations, and then finally another handful of years to specialize, all the while taking on hundreds of thousands of dollars in debt and sacrificing young adulthood. Yet, insidiously, once we have reached the end of the journey, the patient himself is buried underneath our medical knowledge and the disease has seized all our attention.

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Events, Medical Education, Stanford News

TEDMED, in pictures

TEDMED, in pictures

A group of MD and PhD students represented Stanford at TEDMED 2015, which was held last week. Several students have written about their experiences on Scope, and here now are some of their photos from the two-and-a-half-day event.

More photos of Stanford Medicine events, people and places can be found on Instagram.

Photos by Eric Trac, Afaaf Shakir, Chao Long, Lichy Han and Thomas Chew

Big data, Clinical Trials, Events, Research

At TEDMED 2015: Benign drugs? Not under the lens of big data

At TEDMED 2015: Benign drugs? Not under the lens of big data

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here.

xCUEHR0MrJlqiC9phSMFFEjCxjrDDo54Bv0Hc18sYdkPicture this: you go to the doctor and find out that your cholesterol is high. Your doctor prescribes you a medication taken by millions of Americans for lowering cholesterol – Pravastatin. A few months later, you see your doctor again because of persistent depression, and again, you are given a commonly prescribed medication – Paxil.

Russ Altman, MD, PhD, opened his 2015 TEDMED talk with this seemingly innocuous scenario. But through the course of his talk, Altman demonstrated how his lab leveraged big data to reveal the adverse side effects of supposedly benign pharmacological interventions.

When choosing medications for my patients during my clinical rotations, I would often cite evidence from randomized controlled trials about the clinical benefits versus the risks of that particular drug. However, this evidence-based medicine has one major limitation: In clinical studies, patients are usually only on one drug.

My patients, on the other hand, would often come in with bags full of prescription bottles in order to show me which drugs they took, since there were too many medication names to memorize. Often, I found myself wondering quietly, “Is there any way to know if combining these drugs could lead to an adverse event?”

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Events, Medicine and Society

At TEDMED 2015: Behind the glitz, substantive issues

At TEDMED 2015: Behind the glitz, substantive issues

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

TEDMED stage - Lichy HanI admit, I was skeptical heading into the TEDMED conference.

Don’t get me wrong, I love watching TED talks online, and I often listen to Guy Raz on the TED Radio Hour.

However, I’ve always viewed TED primarily as a source of entertainment, a chance to hear fascinating  personal adventures, and the popular science stories that fill us with awe. I’ve thought much less of TED as an entity that could create new knowledge, value and impact beyond storytelling and the occasional self-help guidance.

I’m happy to say that I was wrong.

TED has come under fire from some who paint it as a self-congratulatory echo-chamber of the wealthy elite that counter-productively obfuscates the missions of many speakers by burying their messages in flashy but ultimately meaningless evangelism – “things that make us feel good but which don’t work.” And while, having never attended, I couldn’t share these convictions, the curmudgeon in me could see the logic behind them.

To some extent, those concerns were realized. General admission was $5,000. Speakers were edgily rebranded as “superheroes” or “shepherds,” the kind of visionary titles that might be parodied in an episode of HBO’s “Silicon Valley.” The conference opened with a rock concert and a talk with a main takeaway that seemed to be that female baboons use their male counterparts as sexual objects. There are certainly many important issues embedded in that discussion, but the sensationalist, intentionally provocative delivery came across more Cosmo than Betty Friedan. Sex sells, it seems, even at medical conferences.

But what is it that we’re buying – and is it worth it? I believe so.

As a powerhouse of distributing ideas globally, TED has a social duty to promote not only those ideas that entertain and those that inspire, but also those that disgust, those that depress, and those that make us appreciate. With all eyes upon it, TED can bring some of the most difficult and sensitive, but necessary, topics to the forefront of the conversation.

In particular, I was impressed at the spotlight placed on mental health, an often downplayed and taboo topic that is nevertheless a core element of our profession and school, and my own experiences, friends, and hometown. Pamela Wible, MD, narrated horrifying letters of physician suicide, illustrating great failures in our medical training system. Without TED, few attendees would ever be exposed to these realities. Melissa Walker shared what it was like to have PTSD, and how art therapy could empower veterans to heal when drugs and counseling failed. The Surgeon General himself, Vivek Murthy, MD, chose to focus his TEDMED time on the importance of mindfulness and stress reduction in improving physical and psychiatric outcomes in middle school children.

Many speakers raised concerns about issues ranging from eugenics to institutional racism in healthcare, but what struck me most was how frequently “this is a big problem…” was answered immediately with “…and here’s what we’ve done to fix it…” Activist Raj Patel described how uprooting traditional gender roles was necessary to solve food shortages in Malawi. Bryant Terry recounted teaching nutritional programs to disadvantaged teens in New York. Kenneth Nealson, PhD, a USC professor, and engineer Peter Janicki described new economically sustainable methods that turn sewage and garbage into clean drinking water. All were clear to end with the message “…but there’s a ways to go.”

Is some of the TEDMED glamorization over the top? Absolutely. Are all of the ideas going to radically change the world? Maybe not. But TED has the power to bring people together to share their ideas, to collaborate on new ones, and to showcase their vulnerabilities, failures and unsolved challenges to each other and to the world. That in itself is an idea worth spreading.

Brian Hsueh is an MD/PhD student in neuroscience and bioengineering. He spends his days working on new technologies to understand and treat diseases of the brain, and his nights trying to find economically feasible ways to bring those technologies to patients.

Photo by Lichy Han

Big data, Events, Science

At TEDMED 2015: Using data to maximize human potential

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

A tall, striking woman walked out onto the TEDMED stage. Energetically and confidently, Vivienne Ming, PhD, a theoretical neuroscientist and entrepreneur, went on to tell us about her passion for optimizing human potential utilizing big data.

There are many examples where Ming has used data for social good, such as matching refugees to their families with image-recognition software, but here at TEDMED she discussed personalized education. By looking for trends and patterns in classroom data, she has built an educational tool that predicts a child’s grade trajectory in the class and then chooses the highest impact personalized intervention for each individual student. Using data-science techniques to study society and education, Ming dazzles us with the possibilities of data in improving our capacity to reach our individual potentials.

Ming completely upended my view on data science in social issues

As a graduate student applying these same techniques to the field of genomics, I was intrigued. My understanding of data science applied to the social sciences, such as in the field of economics, was that the modeling remained fairly straightforward and simple: Understandable models were very important for the social sciences, and complex data-science models were not very interpretable. As a medical student, I found this frustrating – my interests lay both in cutting-edge computational advances as well as empathy for human suffering, and I couldn’t figure out how to apply my data-science skills beyond the world of science to answer questions of social and health inequalities.

Ming completely upended my view on data science in social issues. I was fortunate enough to have the chance to chat with her the next day, and I asked her about the computational work, as I was curious how complex her models really could be. She displayed a wonderful technical capacity and a deep understanding of how to choose the right algorithms for the social problems at hand. Granted, it’s still not common to find such imaginative interdisciplinary work combining cutting-edge computer science work and social science work. But Ming showed me a world of possibility around bringing data skills into improving everything from hiring to education to gender equality. I came away impressed, inspired, and excited about the possibilities of utilizing my own skills in the world beyond genomics.

Working at the intersection of two fields can be extremely challenging to impossible. And it’s particularly tricky to apply the latest data-science methods to societal questions. As such, to be able to intelligently and thoughtfully do the two together is an art – and Ming is a master of the important intersection where computation meets humanity.

Daniel Kim is a fifth-year MD/PhD student at Stanford. He studies biomedical informatics and genomics and is interested in all things data-related.

Big data, Cancer, Genetics, NIH, Precision health, Research, Stanford News

“Housekeeping” RNAs have important, and unsuspected, role in cancer prevention, study shows

"Housekeeping" RNAs have important, and unsuspected, role in cancer prevention, study shows

BroomsNot every character in a novel is a princess, a knight or a king. It’s the same for our cellular cast of characters. Most molecules spend their time completing the thousands of mundane tasks necessary to keep our cells humming smoothly. Many of these are referred to as “housekeeping” genes or proteins, and biologists tend to focus their attentions on other, more flashy players.

Now dermatologists Paul Khavari, MD, PhD, and Zurab Siprashvili, PhD, have found that a pair of housekeeping RNA molecules play an important role in cancer prevention. They published their findings yesterday in Nature Genetics.

As I explain in our release:

[The researchers] compared 5,473 tumor genomes with the genomes obtained from surrounding normal tissue in 21 different types of cancer. In many ways, cancer cells represent biology’s wild west. These cells divide rampantly in the absence of normal biological checkpoints, and, as a result, they mutate or even lose genes at much higher rate than normal. As errors accumulate in the genome, things go ever more haywire.

The researchers found that a pair of snoRNAs called SNORD50A/B had been deleted in 10 to 40 percent of tumors in 12 common human cancers, including skin, breast, ovarian, liver and lung. They also noted that breast cancer patients whose tumors had deleted SNORD50A/B, and skin cancer patients whose tumors made lower levels of the RNAs than normal tissue, were less likely than other similar patients to survive their disease.

The researchers used data from the National Institutes of Health’s The Cancer Genome Atlas to find that the RNAs are frequently deleted in tumor tissue. They further went on to show that the RNAs bind an important cancer-associated protein called KRAS and keep it from associating with an activating molecule.

“This is really last thing we would have expected,” said Khavari. “It was particularly surprising because my lab has been studying KRAS intensively for more than a decade, so it was quite a coincidence.”

The researchers believe that understanding more about how the RNAs inhibit KRAS activation could point to possible new therapies for many types of human cancers.

Previously: Listening in on the Ras pathway identifies new target for cancer therapySmoking gun or hit-and-run? How oncogenes make good cells go bad  and Linking cancer gene expression with survival rates, Stanford researchers bring “big data” into the clinic 
Photo by Rob Shenk

Science, Stanford News

A musician amongst the scientists

A musician amongst the scientists

Julie Saiki in her lab - 560

I remember the anxiety I felt during my first college chemistry course. The other students seemed so prepared and confident while I worried about asking an obviously stupid question.

I wonder how much scarier it would have been if I hadn’t taken a full load of science classes in high school? Or if instead of being surrounded by incoming freshman, my classmates included biology, chemistry and engineering graduate students?

This was the situation that Julie Saiki faced when she enrolled in a Stanford’s chemical and systems biology course in drug design and development several years ago. Saiki, a musicology PhD student, had spent her high-school years practicing and performing the violin and viola. After college she lived in Austria for a year, researching 19th and 20th century Austrian chamber music on a Fulbright scholarship. But her career trajectory took a turn. As I wrote in a recent profile article:

Saiki’s plans for a doctorate in musicology were knocked off course after she was diagnosed with ulcerative colitis, a disabling inflammation of the colon. It wasn’t the disease but the cure that sent her in a new academic direction. An herbal remedy put her symptoms into remission, and she went looking for a way to make it available to others. Despite having no science background, she enrolled in a course on drug development; successfully pitched her idea to SPARK, Stanford’s drug development training program; and received approval from the U.S. Food and Drug Administration to begin a clinical trial. Each step brought her cure closer to patients, but the experience, and her success, caused her to re-evaluate her career.

I also describe in the piece the initial thoughts of Daria Mochly-Rosen, PhD, director of SPARK:

Saiki, Mochly-Rosen observed, was a quiet student but whenever she was directly questioned about her group’s progress or approach, her answers were clear and confident. Saiki admits that initially the science lectures were over her head, but her group’s project — a probiotic treatment for Clostridium difficile infections — included market research and how to satisfy regulatory requirements, things Saiki found she could contribute to. She set about to master the individual parts of the process, similar to how she would approach a new piece of music. “You pick things up once you start putting the pieces together,” she said.

Another aspect about Saiki that impressed her mentors at SPARK were her presentation skills. When I talked to her undergraduate violin instructor, Colgate University professor Laura Klugherz, she commented that part of a musician’s training is learning to calm their nerves to the point that they are capable of taking the stage to perform their music beautifully and flawlessly.

I suspect that after playing solo recitals, a room full of scientists isn’t quite so intimidating.

Kim Smuga-Otto is a student in UC Santa Cruz’s science communication program and a former writing intern in the medical school’s Office of Communication and Public Affairs.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development, Ask Stanford Med: Pediatric gastroenterologist taking questions on inflammatory bowel diseases and Stanford Medicine Music Network brings together healers, musicians and music lovers
Photo of Julie Saiki by Norbert von der Groeben

Events, Research, Science, Technology

At TEDMED 2015: Thinking about “breaking through” the valley of death in science

At TEDMED 2015: Thinking about "breaking through" the valley of death in science

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

“I am #BreakingThrough the ‘valley of death.’”

That’s what I wore on my nametag last week at TEDMED. The theme of this year’s conference was “Breaking Through,” and every delegate was asked to write a brief statement that illustrates an area of health care that they’re most passionate about.

The “valley of death” refers to the vast gap in the landscape of biomedical therapeutic development between academia and industry. Traditionally, an academic institution and industry have played two separate but equally important roles in the lengthy and expensive process of bringing new medical innovations to the patient. Academic researchers investigate new mechanisms, pathways and methods, making discoveries that yield promise. Industry then takes these experimental innovations and conducts product development, safety profiling, clinical trials, and manufacturing and distribution, ensuring that extensively tested, safe and efficacious products are widely made available.

However, this transition between academia and industry is not always a smooth one. The pharmaceutical industry is notorious for its extreme risk aversion with new products – and with an average cost of $1B, a 10-year path to FDA approval, and a failure rate north of 95 percent, who can blame them? Meanwhile, most academic labs are neither equipped to nor interested in spending the resources to conduct important yet labor-intensive preclinical work (which, quite frankly, won’t help a scientist graduate, secure tenure, or win a Nobel Prize). And so, because of this, potentially beneficial therapeutics are liable to languish in the valley of death between discovery and human trials.

On Thursday, Stanford professor Daria Mochly-Rosen, PhD, took the TEDMED stage to describe her own experience crossing that valley on the TED stage. In the early 2000s her lab had discovered a novel class of compounds for reducing cardiac injury after heart attack. After receiving universal rejections from pharma companies that they hoped would license the compounds, Mochly-Rosen and one of her graduate students reluctantly took matters into their own hands, left the university, and started KAI Therapeutics to bring their compounds into clinical trials. Long story short, they were eventually wildly successful and acquired by Amgen after demonstrating efficacy in Phase II clinical trials. The experience drove Mochly-Rosen to start the Stanford’s SPARK program, which offers a variety of resources – including classes, industry mentors and grants – to help scientists here survive their own journeys through the valley of death.

As a scientist developing new potential tools for diagnosis and therapy, and as someone who works frequently with early-stage life science companies, I spend a disturbing amount of time thinking about the valley of death. But to me, the valley is much deeper and wider than what it means for pharmaceutical development. It spans similar challenges in medical devices, diagnostics, and even digital health solutions.

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Events, Genetics, Research, Science

At TEDMED 2015: How microbiome studies could improve the future of humanity

At TEDMED 2015:  How microbiome studies could improve the future of humanity

This year’s TEDMED was held Nov. 18-20 in Palm Springs, Calif. Stanford Medicine is a medical research institution partner of TEDMED, and a group of MD and PhD students who represented Stanford at the conference will be sharing their experiences here. 

TEDMED scholarsOne of the highlights at TEDMED for me was meeting and hearing from Chris Mason, PhD, a Weill Cornell Medical College researcher in epigenetics. This is my field of study, so I was excited to talk to someone deeply involved in the world of genomics. Mason was an engaging and fast talking speaker, with a great sense of humor. And I soon discovered that, while he was doing the same sort of work and analysis that I was doing, his samples are incredibly unique.

While I work on primary cell types across the human body, Mason has interesting questions about the microbiome surrounding our body. The cells that make up the microbiome actually outnumber human cells ten times over – and scientists are increasingly gaining an understanding of how the microbiome, individual and personal to each and every person, can have a unique impact on human health and wellness. Mason, knowing this, began to look for interesting and unique ones that could tell us about how these microbiomes could be enhanced and utilized for improving our human lives.

Mason sequenced microbial cells that were gathered from subway riders around the world, and he discovered that about half of the cells discovered were not known microbial species. Literally under our feet, as Mason puts it, there is a world of diversity to explore and the possibility of discovering new antibiotics and cures to disease. But then Mason also went in the other direction – up! – and collected samples from astronauts in space. Now he has access to more than 8,000 samples of astronaut samples (let your imagination wander on what they saved) for a study of the human body in extreme environments.

During Mason’s talk on the last day of the conference, provocatively described by TEDMED organizers as a discussion of how his work is being done “in the interest of humanity’s interplanetary survival,” he touched on the subway experiments as well as the astronaut work, and then tied it all together by talking about the future of humanity. For Mason, an understanding of biology, both microbial and human, is the natural next step in humans’ progress to the stars and beyond. Genetic engineering is already here and will continue to grow as a technology, and he suggested we use it to extend our reach to the moon and beyond. The microbiome could be altered to protect us from UV radiation in space or to help us adapt to new planets, for example. Think of it as an astronaut suit, but biological, he suggested.

Mason’s thoughts may be controversial, depending on what you think about genetics, but he has clearly thought very hard about what new biological technologies mean for humanity’s future. It’s unknown whether the future will develop as Mason has envisioned it, but his work will likely be influential nonetheless.

Daniel Kim is a fifth-year MD/PhD student at Stanford. He studies biomedical informatics and genomics and is interested in all things data-related.

Photo of the author (second from left) and three other TEDMED scholars, from Lichy Han

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