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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.

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

Evolution, Fertility, Pregnancy, Research, Science, Stanford News, Stem Cells, Videos

Viral RNA essential for human development, say Stanford researchers

Viral RNA essential for human development, say Stanford researchers

Viruses are tricky, but we humans may be trickier still. Stanford stem cell biologists Vittorio Sebastiano, PhD, and Jens Durruthy-Durruthy, PhD, published a study today in Nature Genetics indicating that the genetic remnants of ancient viral infections that still linger in our genome are essential to early human embryonic development.

As Sebastiano explained in our release:

We’re starting to accumulate evidence that these viral sequences, which originally may have threatened the survival of our species, were co-opted by our genomes for their own benefit. In this manner, they may even have contributed species-specific characteristics and fundamental cell processes, even in humans.

The researchers, who talk about their work in the video above, relied on a new RNA sequencing technique to investigate the expression of what are called long-intergenic noncoding, or lincRNAs. These molecules don’t contain protein-making instructions, but instead affect the expression of other genes. They’ve been implicated in many important biological processes, including the acquisition of a developmental state called pluripotency that is necessary for a fertilized egg to develop into the cells and tissues of a growing fetus.

More from our release:

They identified more than 2,000 previously unknown RNA sequences, and found that 146 are specifically expressed in embryonic stem cells. They homed in on the 23 most highly expressed sequences, which they termed HPAT1-23, for further study. Thirteen of these, they found, were made up almost entirely of genetic material left behind after an eons-ago infection by a virus called HERV-H.

[…] After identifying HPAT1-23 in embryonic stem cells, Sebastiano and his colleagues studied their expression in human blastocysts — the hollow clump of cells that arises from the egg in the first days after fertilization. They found that HPAT2, HPAT3 and HPAT5 were expressed only in the inner cell mass of the blastocyst, which becomes the developing fetus. Blocking their expression in one cell of a two-celled embryo stopped the affected cell from contributing to the embryo’s inner cell mass. Further studies showed that the expression of the three genes is also required for efficient reprogramming of adult cells into induced pluripotent stem cells.

I can’t stop marveling at the close ties we have with viruses. It makes me think of the words of Michael Corleone in The Godfather: “Keep your friends close, and your enemies closer.” As Durruthy-Durruthy told me, “It’s fascinating to imagine how, during the course of evolution, primates began to recycle these viral leftovers into something that’s beneficial and necessary to our development.”

Previously: My baby, my… virus? Stanford researchers find viral proteins in human embryonic cellsMastermind or freeloader? Viral proteins in early human embryos leave researchers puzzled  and Species-specific differences among placentas due to long-ago viral infection, say Stanford researchers
Video by Christopher Vaughan/Stanford Institute for Stem Cell Biology and Regenerative Medicine

Big data, Biomed Bites, Research, Science

How one statistician is refining clinical trials

How one statistician is refining clinical trials

Biomed Bites is back. It’s a weekly feature that introduces readers to some of Stanford’s most innovative biomedical researchers. 

A love of mathematics propelled Ying Lu, PhD, to his current position as professor of health research and policy – with a specialty in biostatistics.

As the genomic revolution generates skyscrapers of data, biostatisticians like Lu are scrambling to develop more effective and efficient ways to design experiments and conduct clinical trials. Here’s Lu in the video above:

My research focuses on the development and application of novel, cutting-edge biostatistical methods in the evaluation, validation and comparison of new medical diagnoses as well as treatment interventions.

Lu also directs the nearby VA Cooperative Studies Program Coordinating Center, which conducts national clinical trials on topics such as stroke prevention, post-traumatic stress disorder and heart failure treatment.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving biomedical innovation here.

Previously: What I did this summer: Stanford medical student investigates health statistics and costs in Costa Rica, It all comes down to truth: Stanford med student digs in on public-health campaigns and How the FDA is promoting data sharing and transparency to support innovations in public health

Palliative Care, Patient Care, Research, Science, Stanford News

Desire for quality end-of-life care crosses ethnic groups

Desire for quality end-of-life care crosses ethnic groups

VJ in officeEthnic minorities want quality end-of-life care, including in-depth conversations with their physicians about how to achieve this, but they often face barriers to getting the care they desire. That’s according to a study published today in the Journal of Palliative Care.

In a press release I wrote about the study, lead author VJ Periyakoil, MD, a Stanford expert in end-of-life care, explained why she decided it was important to conduct a study with the goal of reaching out to traditionally hard-to-reach ethnic groups within the communities where they live:

There is so much generalization and stereotyping by physicians about how ethnic minorities want everything done, irrespective of how effective these treatments might be at the end of life. I decided that we needed to go into their communities and ask them what they want.

Periyakoil and her colleagues conducted a series of in-person interviews at a scattering of community-based senior centers around the San Francisco Bay Area accompanied by interpreters. The populations are particularly hard to reach because of a number of issues, including language barriers, immigration status, and poverty levels, Periyakoil said. In addition to English, interviews were conducted in Spanish and five Asian languages — Burmese, Hindi, Mandarin, Tagalog and Vietnamese. As I described in the release:

The researchers… found that all participants valued high-quality end-of-life care. A majority, 61 percent, said there were barriers to receiving high-quality care for members of their ethnic group.

The 191 participants who reported barriers to getting quality end-of-life care were asked to describe the biggest barriers, which were, in order of how often they were cited: finances and health insurance; physician behavior; communication problems with doctors; family beliefs; health system barriers; and cultural/religious barriers.

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Ethics, Research, Science, Stanford News

Clues could help identify fraudulent research before publication

Clues could help identify fraudulent research before publication

4443921690_d3b8c60e91_zLiars leave behind evidence, researchers have found, whether they’re bluffing at poker or fabricating financial reports. Now, a study published in the Journal of Language and Social Psychology has identified clues left by researchers who falsify their work.

The study’s authors examined 253 primarily biomedical papers that were retracted from journals for fraud and compared them to papers from the same journals, time periods and publication topics. They developed a “obfuscation index,” which included abstract language, jargon, positive emotional terms, casual language and a reading difficulty score. Fraudulent papers had higher scores than accurate papers, the team found.

A Stanford Report article explains:

“We believe the underlying idea behind obfuscation is to muddle the truth,” said graduate student David Markowitz, the lead author on the paper. “Scientists faking data know that they are committing a misconduct and do not want to get caught. Therefore, one strategy to evade this may be to obscure parts of the paper. We suggest that language can be one of many variables to differentiate between fraudulent and genuine science.”

The results showed that fraudulent retracted papers scored significantly higher on the obfuscation index than papers retracted for other reasons. For example, fraudulent papers contained approximately 1.5 percent more jargon than unretracted papers.

“Fradulent papers had about 60 more jargon-like words per paper compared to unretracted papers,” Markowitz said in the article. “This is a non-trivial amount.”

Previously: New Stanford Medicine magazine explores bioethics, Using social media in clinical research: Case studies address ethical gray areas and “U.S. effect” leads to publication of biased research, says Stanford’s John Ioannidis
Photo by Alan Cleaver

Events, Medical Education, Science

To boost diversity in academia, “true grit” is needed

To boost diversity in academia, "true grit" is needed

photo (1)With evangelical fervor, Freeman Hrabowski, PhD, president of the University of Maryland-Baltimore County (UMBC), challenged the School of Medicine to tackle inequality throughout its ranks, an effort that — if successful — could spill out to benefit society at large.

“It takes effort, being proactive, not being defensive, and being honest and transparent,” Hrabowski told a packed crowd here yesterday. His talk was the part of the Dean’s Lecture Series, which is focused on diversity.

A mathematician, Hrabowski is a national leader in the field of science education and is author of the recently published book, Holding Fast to Dreams: Empowering youth from the Civil Rights crusade to STEM achievement. He was incarcerated during a Civil Rights march in the 1960s and currently campaigns for inclusiveness at all levels of academia.

Dean Lloyd Minor, MD, lauded Hrabowski: “Personally, I have found Freeman to be an enormous source of inspiration, advice and of wisdom in my leadership career. He is an exceedingly wise leader, who measures his leadership by the lives that he impacts.”

Confronting entrenched notions about race and gender and STEM fields (science, technology, engineering and math) won’t be easy, Hrabowski admitted. He said it requires “true grit,” which is also the name of his university’s retriever mascot, True Grit.

One of the most critical points is the first undergraduate science course that high-achieving students take, he said. At UMBC, staff have created a new chemistry center and reorganized the curriculum. It’s also important to upend the cutthroat atmosphere in STEM fields and promote teamwork and cooperation, he said.

As a top institution, Stanford has a responsibility to promote diversity and inclusiveness, Hrabowski told the audience.

“When people look back at Stanford Medicine 100 years from now, who will they say you are?” Hrabowski asked. “The problems we face are more difficult than ever. The challenge is to keep learning and struggling with the issues.”

Previously: Intel’s Rosalind Hudnell kicks off Dean’s Lecture Series on diversity, Former Brown University President Ruth Simmons challenges complacency on diversity and Diversity is initial focus of new Stanford lecture series
Photo by Becky Bach

Chronic Disease, Infectious Disease, Microbiology, Research, Science, Stanford News

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

Bad actors: Viruses, pathogenic bacteria co-star in health-horrific biofilms

biofilmA group under the direction of Stanford infectious disease investigator Paul Bollyky, MD, PhD, has uncovered a criminal conspiracy between two microbial lowlifes that explains how some of medicine’s most recalcitrant bacterial infections resist being expunged.

In a study published today in Cell Host & Microbe, Bollyky and his associates reveal that bacterial pathogens responsible for a big chunk of chronic infections can team up with a type of virus that bacteria ordinarily consider their worst enemies to form biofilms, which, our news release on the study explains, are “slimy, antiobiotic-defying aggregates of bacteria and organic substances that stick to walls and inner linings of infected organs and to chronic wounds, making infections excruciatingly hard to eradicate.” More from that release:

Biofilms factor into 75 to 80 percent of hospital-acquired infections, such as those of the urinary tract, heart valves and knee-replacement prostheses, Bollyky said. “A familiar example of a biofilm is the plaque that forms on our teeth,” he said. “You can brush twice a day, but once that plaque’s in place you’re never going to get rid of it.”

The study first focused on Pseudamonas aeruginosa, which accounts for one in ten hospital-acquired infections, many chronic pneumonia cases and much of the air-passage obstruction afflicting cystic-fibrosis patients.

Cystic fibrosis is deadly mainly because of biofilms formed by P. aeruginosa, Bollyky told me. “These biofilms fill up all the air spaces, and antibiotics can’t seem to penetrate them,” he said.

But he and his colleagues found that P. aeruginosa forms biofilms only when it’s been infected itself.

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