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Applied Biotechnology, Parenting, Pediatrics, Research, Sleep, Stanford News, Technology

Biodesign fellows take on night terrors in children

Biodesign fellows take on night terrors in children

baby on bed

Standing in the Clark Center’s grand courtyard, gazing upward at scientists ascending an outdoor staircase and traversing the exterior corridors on the top two floors, one senses that big ideas take shape here. But how?

Prototyping, say Andy Rink, MD, and Varun Boriah, MS, who spent the last year as Biodesign fellows. Part of Stanford’s Bio-X community, the Biodesign Program trains researchers, clinicians and engineers to be medical-technology innovators during its year-long fellowship. Fellows learn the Biodesign Process, which could be likened to design thinking for health care. On teams of two or four, the fellows identify a substantial health-care need and generate ideas to solve it using medical-device innovation.

Though most Biodesign projects take root after fellows complete a “clinical immersion” shadowing health-care workers in a hospital to observe problems, Rink found his inspiration when visiting family and waking up to a 3-year-old relative’s screams from recurring night terrors. The problem was not so much that it affected the child – pediatricians may advise that children will likely outgrow the condition – but that it affected the parents, Rink saw.  The parent’s lost sleep and anxiety over their child’s well being had huge effects on their quality of life. (In some cases, these are so severe that Xanax and Valium may be prescribed to the children as a last-ditch effort.) What if a treatment could be found that involved no medication and no parental intervention, offering everyone a solid night’s sleep?

The physician and engineer are working with School of Medicine sleep researchers Christian Guilleminault, MD, professor of psychiatry and behavioral sciences, and Shannon Sullivan, MD, clinical assistant professor of psychiatry and behavioral sciences, on a clinical method to treat night terrors in children. In a first-floor room of the Clark Center, they’re protoyping an under-mattress device that senses how deeply a child is sleeping and is able to prevent the nightly episodes from occurring, creating a healthier sleep cycle for the children.  This relieves the parent’s anxiety, and helps the entire family sleep better.

Faculty and students from more than 40 departments across Stanford’s campus, including the schools of medicine, business, law, engineering and humanities and sciences, play a role in Biodesign, as do experts from outside the university. Fellows work closely with the Institute of Design at Stanford, attending – and then teaching – the school’s d.bootcamp. They also have access to the d.school’s facilities and consult regularly with their faculty. Some of the d.school’s methods – focusing on big problems, encouraging radical collaboration, prototyping early and user-testing before focusing on functionality – guide the trajectory of Biodesign projects.

Physicians who are Biodesign fellows often work outside their specialty, and engineers bring a mix of academic and industry experience to the design table. While faculty mentors may simply provide advice to fellows, Guilleminault and Sullivan have become invested in the course of the research as lead investigators on the study. For their involvement, they were both honored with the Biodesign Specialty Team Mentorship Award.

Fellow Boriah noted that medical-device innovation is moving from products like catheters to systems such as health IT, mobile health and software. A former CEO and co-founder of a wearable patient blood-diagnostics device, he said the Biodesign program has provided valuable “access to clinical reality.” Rink, a surgical resident at Northwestern University, said that as a fellow, he’s been “exposed to a side you don’t see in a hospital.”

The researchers are currently recruiting participants ages 2-12 for their study. Rink and Boriah are also working with the Stanford-supported StartX to see their project into the next stage of development.

Previously: Sleep, baby, sleep: Infants’ sleep difficulties could signal future problemsStudying pediatric sleep disorders an “integral part” of the future of sleep medicine and At Med School 101, teens learn that it’s “so cool to be a doctor” 
Photo by MissMayoi

Applied Biotechnology, Ophthalmology, Public Health, Stanford News, Technology

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

Stanford-developed eye implant could work with smartphone to improve glaucoma treatments

eyeGlaucoma, caused by rising fluid pressure in the eyes, is known as the silent thief of sight. Catching the disease in the early stages is critical because if detected too late it leads to blindness. Regular monitoring and controlling of the disease once detected is invaluable.

Now, Stephen Quake, PhD, professor of bioengineering at Stanford, and Yossi Mandel, MD, PhD, an applied physics and ophthalmologist at Bar-Ilan University in Israel, have developed a tiny eye implant that would allow patients to take daily or hourly measurements of eye pressure from home.

A recent Stanford Report article explains how the device works:

It consists of a small tube – one end is open to the fluids that fill the eye; the other end is capped with a small bulb filled with gas. As the [internal optic pressure] increases, intraocular fluid is pushed into the tube; the gas pushes back against this flow.

As IOP fluctuates, the meniscus – the barrier between the fluid and the gas – moves back and forth in the tube. Patients could use a custom smartphone app or a wearable technology, such as Google Glass, to snap a photo of the instrument at any time, providing a critical wealth of data that could steer treatment. For instance, in one previous study, researchers found that 24-hour IOP monitoring resulted in a change in treatment in up to 80 percent of patients.

“For me, the charm of this is the simplicity of the device. Glaucoma is a substantial issue in human health. It’s critical to catch things before they go off the rails, because once you go off, you can go blind. If patients could monitor themselves frequently, you might see an improvement in treatments,” Quake added.

The full report (subscription required) is published in the current issue of Nature Medicine.

Jen Baxter is a freelance writer and photographer. After spending eight years working for Kaiser Permanente Health plan she took a self-imposed sabbatical to travel around South East Asia and become a blogger. She enjoys writing about nutrition, meditation, and mental health, and finding personal stories that inspire people to take responsibility for their own well-being. Her website and blog can be found at www.jenbaxter.com.

Previously: What I did this summer: Stanford medical student investigates early detection methods for glaucomaTo maintain good eyesight, make healthy vision a priority and Instagram for eyes: Stanford ophthalmologists develop low-cost device to ease image sharing
Photo by Magmiretoby

Applied Biotechnology, Stanford News, Videos

Drew Endy discusses the potential to program life and future of genetic engineering at TEDxStanford

Drew Endy discusses the potential to program life and future of genetic engineering at TEDxStanford

In 2013, Drew Endy, PhD, assistant professor of bioengineering, was honored as a Champion of Change by the White House. A leader in the field of synthetic biology, Endy founded BioBricks Foundation, which has underwritten an open technical-standards-setting process for synthetic biology and developed a legal contract for making genetic materials free to share and use. He spoke at TEDxStanford about his work with designers, social scientists and others to transcend the industrialization of nature. Watch the above video to learn more about the potential for making life programmable and the future of genetic engineering.

Previously: Programming cells for chemical production and disease detection, The “new frontier” of synthetic biology, Drew Endy discusses developing rewritable digital data storage in DNA and Researchers create rewritable digital storage in DNA

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

Manu Prakash on how growing up in India influenced his interests as a Maker and entrepreneur

Manu Prakash on how growing up in India influenced his  interests as a Maker and entrepreneur

foldscope_6.23.14Last week, Stanford bioengineer Manu Prakash, PhD, inventor of the 50-cent microscope, called the Foldscope, and a $5 chemistry kit, participated in the White House’s first-ever Maker Faire.

In a Q&A recently published on the White House blog, Prakash discusses what led him to become a Maker, his journey to the United States from India to pursue science and how he hopes his inventions will change the world. On the topic of how his immigrant roots influenced his interests as a Maker and entrepreneur, he says:

I recently started my own lab in the U.S. I decided to dedicate half of my time to frugal science (in the night time, I am a marine biophysicist). Because of growing up in a developing country context with very little resources, I naturally understand the scale of problems and the scale of solutions needed. But only by being in the hyperdrive mode of innovation in the U.S. do I have the tools at hand to actually tackle these challenges. So what I am as a Maker, an entrepreneur, and as an academic scientist is truly a juxtaposition/superposition of my experiences in these two countries.

Another common thread that my Indian roots taught me, which got strengthened by my experiences in the United States, is empathy. Without it, all the technological innovation in the world will not be utilized. It’s humans that make this incredible machine we call society run. The current society is truly global and we need to be global scientists.

Previously: Dr. Prakash goes to Washington, Stanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries and Free DIY microscope kits to citizen scientists with inspiring project ideas
Photo by @PrakashLab

Applied Biotechnology, Bioengineering, Science, Stanford News, Technology

Dr. Prakash goes to Washington

Dr. Prakash goes to Washington

Prakash at White House

It’s not every day that a researcher gets to hang out at the White House – so Wednesday was rather unusual for Stanford bioengineer Manu Prakash, PhD. Prakash, inventor of the 50-cent microscope, called the Foldscope, and a $5 chemistry kit, participated in the White House’s first-ever Maker Faire that day. He called it an “inspiring event” and tweeted the above photo from his time there.

And for those interested in learning more, a paper on the Foldscope was published online this week in PLOS One.

Previously: Stanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries, Free DIY microscope kits to citizen scientists with inspiring project ideas and Stanford bioengineer develops a 50-cent paper microscope
Photo by Manu Prakash

Applied Biotechnology, Bioengineering, Science, Science Policy, Stanford News

Stanford microscope inventor invited to first White House Maker Faire

Stanford microscope inventor invited to first White House Maker Faire

Foldscope-adams-squareLast week assistant professor of bioengineering Manu Prakash, PhD, received a call he couldn’t refuse — an invitation to attend the first-ever White House Maker Faire, to show attendees how to build a 50-cent microscope out of laser-cut paper, plastic tape and a tiny glass bead.

At today’s event, Prakash will also demonstrate how he turned a toy music box into a $5 programmable microfluidic chemistry set that can be used for applications as diverse as testing water quality and science fair projects.

Maker Faires, started by Make magazine in 2006, are gatherings where do-it-yourself enthusiasts show off their homemade projects and teach others how to make things using new technologies such as 3D printers, laser cutters, and desktop machine tools.

President Obama is hosting the first-ever White House Maker Faire to celebrate our “Nation of Makers” and to help empower America’s students and entrepreneurs to invent the future.

Prakash, who grew up in the mega-cities of India without a refrigerator, is a leader in the frugal maker movement. At Stanford, he works with students from bioengineering, medicine, and Bio-X to reengineer expensive, complex health-related devices to make them better, faster and cheaper.

His team also focuses on developing affordable science tools to inspire global innovation. To that end, Prakash recently launched an educational initiative called the “10,000 Microscopes Project,” where build-your-own-microscope kits will be shipped to the first 10,000 people who pledge to share their microscope images and experiments in a free, online microscopy manual.

“I’m so happy that the White House is looking at ways to celebrate scientific curiosity and invention,” Prakash told me. “Many children around the world have never used a microscope, even in developed countries like the United States. A universal program providing a microscope for every child could foster deep interest in science at an early age.”

For more information on the White House Maker Faire and today’s National Day of Making, or to watch the event live, visit www.whitehouse.gov/makerfaire or follow #NationofMakers on Twitter.

Previously: The pied piper of cool science tools, Music box inspires a chemistry set for kids and scientists in developing countries, Free DIY microscope kits to citizen scientists with inspiring project ideas and Stanford bioengineer develops a 50-cent paper microscope
Photo, of Quinn Monahan trying out a paper microscope, by Amy Adams
Photo in featured entry box by Manu Prakash

Applied Biotechnology, Cancer, Genetics, otolaryngology, Research, Stanford News

Stanford researchers identify genes that cause disfiguring jaw tumor

Stanford researchers identify genes that cause disfiguring jaw tumor

jawPatients with the rare jaw tumor ameloblastoma have few treatment choices. Radiation and drugs have failed to stop this slow-growing cancer, leaving jaw removal as the only option. The surgery also takes out facial nerves and blood vessels, and so patients need reconstructive surgery and rehabilitation just to smile and chew again.

In a new study, published in Nature Genetics, Stanford researchers discovered two gene mutations that cause this tumor. Their findings point to FDA-approved drugs that are effective against these mutations in other types of cancer.

To find the mutations, the researchers sequenced mRNA – messages copied from genes that tell the cell how to make proteins – from slices of preserved tumor. In 80% of the samples, they found a mutation in either the SMO or the BRAF gene. Interestingly, the SMO mutations occurred predominantly in the upper jaw, while BRAF mutations were found mainly in the lower jaw.

From our press release:

“These genes are essential for delivering signals of growth and development, particularly in developing organs,” said Robert West, MD, PhD, associate professor of pathology at Stanford and a senior author on the study. “But it’s increasingly apparent that they are often mutated in cancers.”

Perhaps most promising, researchers found that there are already FDA-approved drugs for cancers with mutations in the same developmental pathway. A drug called vemurafenib is toxic to ameloblastoma cell cultures that harbor a BRAF mutation, they found. This drug is effective against melanomas that carry the same mutant gene. Researchers also found that a compound called arsenic trioxide, an approved anti-leukemia drug, is affective at blocking the mutant SMO protein.

West and his colleagues, A. Cain McClary, MD, a co-author and chief pathology resident at Stanford Hospital, and A. Dimitrios Colevas, MD, an associate professor of oncology at Stanford, have already submitted an application to the biotech company Genentech, which manufactures the most popular brand of vemurafenib. Their pilot study would test whether the drug could shrink tumors in people with ameloblastomas.

Also from the release:

Throughout this project, McClary has engaged with an ameloblastoma Facebook group to hear members’ stories and to learn about what a patient goes through during the initial surgery and subsequent facial reconstruction. He plans to conduct a webinar with the group, and can’t wait to share his findings with them.

“It’s a great motivator,” he said about his involvement with the group. “Our face is a special place. I couldn’t imagine not smiling.”

Patricia Waldron is a science writing intern in the medical school’s Office of Communication & Public Affairs.

Previously: Gene panel screens for dozens of cancer-associated mutations, say Stanford researchers
Photo by Gray’s Anatomy Plates/Wikimedia Commons

Applied Biotechnology, Events, Infectious Disease, Research, Stanford News, Videos

Stanford microbiologist’s secret sauce for disease detection

Stanford microbiologist's secret sauce for disease detection

Last week, John Boothroyd, PhD, kicked off Stanford’s first Disease Detective lecture series with a fascinating tale about how his lab invented a simple biochemical “secret sauce” that revolutionized the detection of viral and bacterial infections like HIV, Hepatitis C and gonorrhea.

“It mostly started as a sketch on a piece of paper, then later became Gen-Probe’s core technology, which won them the 2004 National Medal of Technology,” explained Boothroyd, a Stanford professor of microbiology and immunology.

What Boothroyd invented, in collaboration with postdoctoral researchers James Burg and Philippe Pouletty, is called Transcription-Mediated Amplification.

Before this discovery, detecting a snippet of disease-specific DNA in a sample of cells was like finding a needle in a haystack. To increase a test’s accuracy, a lab technician would try to coax the target DNA into replicating itself through hours of tedious time-and- temperature-sensitive steps.

Boothroyd and his team’s new process consisted of a simple recipe of primers and enzymes that, after optimization by Gen-Probe, tricked a target snippet of DNA into automatically creating 10 billion copies of itself in less than an hour. This ultimately enabled the development of cheaper and faster disease tests.

In 2012 Boothroyd was ushered into the Stanford Inventor’s Hall of Fame because of this patent, which is among the top-ten revenue-generating inventions Stanford. He has six other patented inventions, including one that makes antigen production for the testing of toxoplasmosis infections far more efficient. Another detects toxoplasmosis in the amniotic fluid of pregnant women. He describes this research in the video above.

Looking back on his career choices, one thing that Boothroyd is grateful for is being able to combine his two loves at Stanford — basic research and teaching — while leaving the business of running a company to his patent licensees.

To the lecture hall filled with student researchers worried about the “postdocalypse,” the shortage of tenure-track research positions in academia, he gave this advice:

“I think the [postdocalypse] negativity is overstated. You have to have faith in yourself. You have to do what you want to do. If you’re enjoying your work and it’s a stepping stone to where you’re going, relax and see what happens.”

The next Disease Detective lecture will be held during fall quarter 2014. Watch for details on the Stanford Predictives and Diagnostics Accelerator webpage.

Previously: Patrick House discusses Toxoplasma gondii, parasitic mind control and zombies, Cat guts, car crashes, and warp-speed Toxoplasma infections, and NIH study supports screening pregnant women for toxoplasmosis

Applied Biotechnology, Clinical Trials, FDA, Public Health, Research, Stanford News

The best toxicology lab: a mouse with a human liver

The best toxicology lab: a mouse with a human liver

of mice and menA few years ago, Stanford pharmacogenomic expert Gary Peltz, MD, PhD, collaborating with researchers in Japan, developed a line of bioengineered mice whose livers were largely replaced with human liver cells that recapitulate the architecture and function of a human liver. Now, in a recent study published in PLoS Medicine, Peltz’s team has shown that routine use of this altered lab mouse in standard toxicology tests preceding clinical trials would save human lives.

Among the liver’s numerous other job responsibilities, one of the most important is chemically modifying drugs in various ways to make them easier for the body to get rid of. But some of those chemical products, or metabolites, can themselves be quite toxic if they reach high levels before they’ve been excreted.

The Food and Drug Administration requires that prior to human testing, a drug’s toxicological potential be assessed in at least two mammalian species. But we humans metabolize things differently from other mammals, because our livers are different. That can make for nasty surprises. All too often, drugs showing tremendous promise in preclinical animal assessments fail in human trials due to unforeseen liver toxicity, said Peltz, a former pharmaceutical executive who is intimately familiar with established preclinical testing procedures in the industry.

That’s what happened in 1993 when, after a short safety trial of a drug called FIAU concluded without incident, the comp0und was placed in a phase-2 clinical trial of a drug for hepatitis B. FIAU belongs to a class of drugs that can interfere with viral replication, so it was considered a great candidate for treating virally induced infections such as hepatitis B.

As I wrote in my release about the new study:

“FIAU was supposed to be a revolutionary drug,” Peltz said. “It looked very promising in preclinical tests. In phase 1, when the drug was administered to subjects for a short period of time, the human subjects seemed to do fairly well.” But the phase-2 trial was stopped after 13 weeks, when it became clear that FIAU was destroying patients’ livers.

In fact, nearly half the patients treated with FIAU in that trial died from complications of liver damage. Yet, before advancing to clinical trials FIAU had been tested for as long as six months in mice, rats, dogs and monkeys without any trace of toxicity. An investigation conducted by the National Academy of Sciences later determined that the drug had shown no signs of being dangerous during those rigorous preclinical toxicology tests.

In Peltz’s new study, though, FIAU caused unmistakable early signs of  severe liver toxicity in the bioengineered mice with human livers. This observation would have served as a bright red stop signal that would have prevented the drug from being administered to people.

Bonus item: Using bioengineered mice with human livers instead of mice with murine ones would no doubt result in the clinical and commercial success of some drugs that never got to the human-testing stage because they caused liver toxicity in mice.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, Alchemy: From liposuction fluid to new liver cells and Immunology escapes from the mouse trap
Photo by erjkprunczyk

Applied Biotechnology, Bioengineering, Global Health, Microbiology, Science

The pied piper of cool science tools

The pied piper of cool science tools

Kid-scopeWhen Stanford bioengineer Manu Prakash, PhD, and his students set out to solve a challenging global health problem, the first order of business is to have fun.

“We’re a curiosity-driven lab,” says Prakash, as he sits in his office overflowing with toys, gadgets, seashells and insect exoskeletons.

In the last month, Prakash introduced two new cool science tools — a 50-cent paper microscope and a $5 programmable kid’s chemistry set. The response from fellow science lovers, compiled on this Storify page, has been amazing.

Already, 10,000 kids, teachers, health workers and small thinkers from around the globe have signed up to receive build-your-own-microscope kits. Thousands more have sent us e-mails describing the creative ways they’d use a microscope that they could carry around in their back pockets.

For the love of science, here are a few of these inspirational e-mails:

I would love to have one. I’m only in 6th grade but I love science. I hope to visit the moon one day. — Raul

I am an electrical engineer from Kenya and have never used a microscope in all my life. But what I would really like to do is to avail the foldscope to students in a primary school that I am involved in mentoring. This apart from hopefully inspiring them in the wonders of science, would enable the students see the structure of the mosquito proboscis, a malaria-spreading agent in this part of the world. I would also like to look at the roots of mangrove trees and see the structure that enables them to keep sea water salts out. — Macharia Wanyoike

This is brilliant! I am in science and nanotechnology education and my wish is for South African rural children, Namibia, Zimbabwe, Botswana to all have these microscopes! It will be amazing. — Professor Sanette Brits, University of Limpopo, South Africa

waterbearI am studying how magnetic fields at different frequencies affect water bears. They are very difficult to find and it would be great if I had a tool to help me find them that is  portable while searching for them. I have digital motic microscope phase contrast and darkfield microscopes but nothing portable. — Edward W. Verner (Water bear shown to the left.)

I could use it to check if patients have scabies. Or if I were visiting remote monasteries in the Himalayas where they have outbreaks. I’d definitely pack it. For myself I’d use it on nature walks. GREAT ACCOMPLISHMENT for mankind. Congratulations. — Linda Laueeano, RN

Hi! I am a high school student from South Korea. While I was searching for interesting project, I saw your video. It was very amazing and I can’t believe that only one dollar can save hundreds and thousands people who were suffering from malaria and other diseases that can be found by your “foldscope”. I really love to study about your project and I had already read your thesis. Truly, it was hard to understand everything, but I really tried hard and I discussed this issue for more than a week with my science club. We are group of 10 people and we are eager to do this project. Also I really appreciate you to do this wonderful thing for poor kids in many other countries. Thanks. — Joung Yeon Park

I am assisting a K-12 community school with creating a STEAM Innovation Knowledge HUB, as they are trying to move their Common Core Curriculum into a STEM to STEAM driven program. It would be great to receive several Foldscopes or be able to purchase. Please contact me ASAP. Congratulations on a great new support product and great innovation. Thank you, smile. — Dr. Dion N. Johnson, Wayne State University

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