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Bioengineering, Cancer, Infectious Disease, Precision health, Research, Stanford News

Stanford scientists co-opt viral machinery to create medical delivery system

Stanford scientists co-opt viral machinery to create medical delivery system

James Swartz

Stanford engineering researcher James Swartz, PhD, and his colleagues have remodeled a hepatitis B virus to turn it into a microscopic taxi for medical therapies. The team stripped the virus of its pathogenic DNA and modified an outer shell so that they could “hang” molecular tags on the outside to help deliver vaccines or other therapies to specific cells. The researchers reported their findings in a paper in the scientific journal Proceedings of the National Academy this week.

They call the engineered product a virus-like particle (as opposed to a real virus with infectious material) or a smart particle. “We make it smart by adding molecular tags that act like addresses to send the therapeutic payload where we want it to go,” Swartz said in a Stanford News story.

The smart particle is a novel way to deliver vaccines or cancer therapies by teaching the body’s immune cells to recognize pathogens or cancer cells. Alternatively, the smart particle can deliver medicine specifically to the cells that need it.

Swartz and his colleagues’ effort is part of a larger field of targeted therapies that aims to precisely deliver therapies to the cells that need them and avoid damaging nearby healthy cells. Current cancer therapies, for example, are effective at fighting malignant cells, but also kill off healthy cells. That’s why cancer therapies often have such devastating side effects. But previous attempts to create virus-sized delivery systems have not been successful. In fact, Swartz’s team had a hard time getting funding for the early stages of this project because of previous failed efforts by other scientists.

So far, Swartz and colleagues have created the self-assembling shell that is invisible to the body’s natural immune defenses and strong enough to weather conditions in the blood stream and get its packaged contents to its destination inside the body. Next, they’ll work on putting specific cancer-fighting tags on the shell.

The most challenging task will be to pack the shell with a tiny dose of medicine. But Swartz sounded optimistic about his team’s goals. “I believe we can use this smart particle to deliver cancer-fighting immunotherapies that will have minimal side effects,” he said.

Previously: A less toxic, targeted therapy for childhood brain cancerIs cancer too complex for targeted therapies? and Working to create a universal flu vaccine
Photo, of Swartz holding an enlarged replica of a virus-like particle, by Linda Rice

Bioengineering, Cancer, Genetics, Stanford News

Cancer drug produced in common plant

Cancer drug produced in common plant

I knew that many of the drugs we use today were first identified in plants. What I didn’t know was in how many cases those plants are still the only source of the drug because scientists haven’t figured out how to make them in the lab.

If the only source of an effective drug is a plant that is rare, endangered, or hard to grow in the lab, that’s obviously a problem.

Elizabeth Sattely, PhD, a Stanford chemical engineer, recently tackled this problem for a popular cancer drug that comes from a Himalayan plant called the Mayapple. She managed to identify the ten drug-making enzymes in the Mayapple and insert those genes into a much easier-to-grow plant. In a story about the work, which appears today in the journal Science, I wrote:

[It] could lead to new ways of modifying the natural pathways to produce derivative drugs that are safer or more effective than the natural source.

“A big promise of synthetic biology is to be able to engineer pathways that occur in nature, but if we don’t know what the proteins are, then we can’t even start on that endeavor,” said Sattely, who is also a member of the interdisciplinary institutes Stanford Bio-X and Stanford ChEM-H.

Sattely said this is really a first step. Ultimately she’d like to get those same enzymes into yeast, which can produce high volumes of drugs in big laboratory vats.

Video by Amy Adams

Bioengineering, Research, Stanford News, Technology

New Stanford-developed technology bypasses “virtual reality sickness”

New Stanford-developed technology bypasses "virtual reality sickness"

headset_newsResearchers in the Stanford Computational Imaging Group have developed a new virtual reality headset that takes into account how the human eye focuses and processes depth.

Current display technologies are essentially two-dimensional and don’t present images the way our eyes were designed to see them, which can cause “virtual reality sickness,” or VR sickness for short, after only a few minutes.

The new system involves two transparent LCD displays with a spacer in between, which is called “light field technology.” A Stanford News article describes a light field as creating “multiple, slightly different perspectives over different parts of the same pupil. The result: you can freely move your focus and experience depth in the virtual scene, just as in real life.”

Gordon Wetzstein, PhD, assistant professor of electrical engineering, developed the technology along with researchers Fu-Chung Huang and Kevin Chen. In the news piece, Wetzstein listed the variety of applications this advance could have, robotic surgery top among them: “If you have a five-hour [robotic] surgery, you really want to try to minimize the eye strain that you put on the surgeon and create as natural and comfortable a viewing experience as possible.”

But the applications aren’t limited to what has already been imagined. Wetzstein explains, “Virtual reality gives us a new way of communicating among people, of telling stories, of experiencing all kinds of things remotely or closely. It’s going to change communication between people on a fundamental level.”

You can access a short video on the new development here.

Previously: Fear factor: Using virtual reality to overcome phobias, From “abstract” to “visceral”: Virtual reality systems could help address pain, Double vision: How the brain creates a single view of the world, Discover magazine looks at super human vision and Augmented reality iOS app for color vision deficiency
Photo by Vignesh Ramachandran

Bioengineering, Cancer, Imaging, Microbiology, Research, Science, Stanford News

Stanford team develops technique to magnetically levitate single cells

Stanford team develops technique to magnetically levitate single cells

Remember the levitating frog? That feat — the levitation of a live frog using a powerful magnet — was awarded the 2000 Ig Nobel Prize. Fascinating to watch, the demonstration also cemented a longstanding belief that levitating anything smaller than 20 microns was flat-out impossible. Much less something alive.

Not so, a team of Stanford-based researchers showed in a paper published today in the Proceedings of the National Academy of Sciences (PNAS). Using a 2-inch-long device made of two magnets affixed with plastic, the team showed it’s possible to levitate individual cells.

The video above demonstrates the technique in a population of breast cancer cells. Originally, the cells hover, suspended between the two magnets. But when exposed to an acid, they start to die and fall as their density increases.

“It has very broad implications in multiple diseases including cancer, especially for point-of-care applications where it can bring the central lab diagnostics to the comfort of patients’ homes or physicians’ office,” Utkan Demirci, PhD, a co-senior author and associate professor of radiology, told me.

The technique makes it possible to distinguish healthy cells from cancerous cells, monitor the real-time response of bacteria or yeast to drugs and distinguish other differences between cells that were thought to be homogenous, said Naside Gozde Durmus, PhD, a postdoctoral research fellow and first author of the paper.

Critically, the technique does not require treating the cells with antibodies or other markers, Durmus said. That ensures the cells are not altered by any treatments and makes the technique easy to use in a variety of settings, including potentially in physicians’ offices or in resource-poor settings.

The device works by balancing the gravitational mass of a cell against its inherent magnetic signature, which is negligible when compared with the cell’s density, Durmus said.

Interestingly, however, the cells — or bacteria treated with an antibiotic — do not die at the same rate, providing hints at their individual adaptations to environmental stressors, said co-senior author Lars Steinmetz, PhD, a professor of genetics.

To enhance the precision of the technique, the researchers can tweak the concentration of the solution that holds the cells, Durmus said. A highly concentrated solution allows for the differentiation of cells of similar densities, while a less concentrated solution can be used to examine a population of heterogeneous cells.

The team plans to investigate the applications of the device next, including its use in resource-poor settings where the cells can be observed using only a lens attached to an iPhone, Durmus said.

Previously: Harnessing magnetic levitation to analyze what we eat, Researchers develop device to sort blood cells with magnetic nanoparticles and Stanford-developed smart phone blood-testing device wins international award
Video courtesy of Naside Gozde Durmus

Bioengineering, Cardiovascular Medicine, Global Health, Stanford News, Technology

Stanford-India Biodesign co-founder: “You can become a millionaire, but also make a difference”

Stanford-India Biodesign co-founder: "You can become a millionaire, but also make a difference"

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

4499846308_9f084d26f0_zThe three Indian biodesign fellows who were at Stanford for the past six months have returned to New Delhi, where they’ll finish up their fellowship. They’re the last class of fellows from the Stanford-India Biodesign program, and in India they’ll be joining two teams already in progress as part of the new School of International Biodesign (SIB).

Balram Bhargava, MD, executive director of Stanford-India Biodesign (India), was at Stanford for the fellow’s final presentation of their prototype. He helped establish the relationship between Stanford and India and is now revamping the new self-sufficient program.

How did Stanford-India Biodesign originate?

I was at a retirement party in September 2006 for Ulrich Sigwart, MD, who developed the first stent. He called in some friends from all over the world, including Paul Yock, MD (director of the Stanford Biodesign Program). Paul and I shared a taxi ride to Ulrich’s vacation home and got talking. That’s when the program started. By January 2008 the first batch of fellows was here.

The basic intent was to start this innovative program in India and ultimately make it self-sufficient. We selected students from India and sent them to Stanford, then they finished out their fellowship in India.

How has the program changed over the years?

Our early fellows returned from Stanford with high-end ideas such as robots. I had to pull them all down back to the ground. My role was to give this program a soul, and I think I have been successful at that. After a few years Stanford also accepted that frugal design was the right thing for the world and I’m happy about that.

Many of our students had the intention of setting up a company and becoming millionaires. We’ve given them the idea that you can become a millionaire, but at the same time you can make a difference. That’s the delicate balance we want to teach. The students have been very bright and many of them have really delivered on this dream.

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Bioengineering, Neuroscience, Stanford News, Technology

From brains to computers: How do we reverse-engineer the most mysterious organ?

From brains to computers: How do we reverse-engineer the most mysterious organ?


So let’s say you want to make a piece of electronics that works just like the brain. Where would you start?

That’s the question neuroscientist Bill Newsome, PhD, director of the Stanford Neurosciences Institute, posed in a recent talk to a Worldview Stanford class on decision-making.

I thought the idea was so intriguing I wrote a series of stories about what it would take to reverse engineer the brain, and how close we are to succeeding at each. We’re still a ways from computers that mimic our own agile noggins, but a number of people are making progress in everything from figuring out where the brain’s wiring goes to creating computers that can learn.

These are the steps Newsome outlined to take us from our own grey goo to electronics with human-like capacities:

  1. Map the connections: Neuroscientists Karl Deisseroth, MD, PhD, and Brian Wandell, PhD, are mapping where the brain’s 100 billion neurons go.
  2. Monitor the signals: Biologist Mark Schnitzer, PhD, and bioengineer Michael Lin, MD, PhD, have created ways of watching signals in real time as they fire throughout the brain
  3. Manipulate the system: Neuroscientists Karl Deisseroth, MD, PhD, and Amit Etkin, MD, PhD, are working on techniques to manipulate the way the brain works and watch what happens.
  4. Develop a theory: Not only do we not know how the brain works, we don’t even really have a theory. Applied physicist Surya Ganguli, PhD, is working to change that.
  5. Digitize the circuits: If you want to turn the brain into electronics you need some wiring that mimics the brain. Bioengineer Kwabena Boahen has made just such a chip.
  6. Teach electronics to interact: Engineer Fei-Fei Li, PhD, has taught a computer to recognize images with almost human-like precision. This kind of ability will be needed by electronics of the future like self-driving cars or smarter robots.

Previously: Neuroscientists dream big, come up with ideas for prosthetics, mental health, stroke and more
Image, based on two Shutterstock images, by Eric Cheng

Bioengineering, Global Health, Stanford News, Technology

Success breeds success: Early innovators in India created a sense of possibility

Success breeds success: Early innovators in India created a sense of possibility

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

MATERNAL & INFANT MORTALITY IN DEVELOPING COUNTRIESAnurag Mairal, PhD, MBA, director of global exchange programs, joined Stanford-India Biodesign in 2008 to help fellows navigate challenges in designing new medical technology in India, which at the time had great need but little infrastructure for developing and marketing new technologies. I recently spoke with him about the program.

What were the challenges for Biodesign in India when you started?

When I joined Stanford-India Biodesign I felt it was going to be a difficult ride knowing India at that time. The mindset in India is very traditional and doesn’t allow people to step out of the box. Here in the United States what is remarkable is that we have everything across the street. Design, prototypes, animal labs, testing facilities, venture capital — they are all easily accessible. In India none of that existed. We needed to build all of that because it was going to be important to the success of Biodesign.

I had experience in emerging markets and was able to step in when the fellows needed to start thinking about markets for their products. I had a good understanding of the needs and also what challenges a typical medical device would face.

Have things changed?

One of the remarkable things that happened is that not only was the program successful, it affected other institutions in India in both the private sector and academia. A lot of innovators are now working on new technologies across India. Now we need to help all of them with commercializing the technology.

Success breeds success. When one group has success developing a medical technology it makes other people believe it is possible. That sense of possibility and reality has been a major accomplishment. The success of the early fellows and the ecosystem we built around them brought people together and energized the following batches of innovators. Now there is no doubt that medical device innovation is a real thing in India. It’s a remarkable shift in tone in that marketplace.

What is next for Stanford-India Biodesign now that fellows won’t be spending extensive time at Stanford?

Phase 1 of Stanford-India Biodesign was training fellows in the Biodesign process. Most of those previous fellows are in development mode now, and we see challenges in commercializing their products. I think there is a lot of work that needs to happen before these technologies are successful in the marketplace in India. Phase 2 will focus on training entrepreneurs and innovators on the entire process of developing and commercializing a product.

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Bioengineering, Global Health, Medicine and Society, Research, Stanford News, Technology

National Geographic: “Emerging Explorer” Manu Prakash helping “lead a new age of discovery”

National Geographic: "Emerging Explorer" Manu Prakash helping "lead a new age of discovery"

Prakash in Nigeria - 560

As I’ve gotten busier, and my life has moved online, I’ve let most of my magazine subscriptions lapse. All except for National Geographic, which both my husband and I continue to enjoy each month.

With its storied history, familiar yellow cover, knock-your-socks-off photography and carefully crafted science and social science features, I consider it a good use of precious paper (and pennies).

So I was psyched to hear that Stanford’s own Manu Prakash, PhD, has been named by the publication as one of 14 2015 National Geographic Emerging Explorers. Prakash is most well-known for the Foldscope, a low-cost paper microscope that has been sent to 130 countries, but he’s also working on constructing a small-scale chemistry kit and on a variety of other projects. As summarized in a National Geographic article, he “specializes in what he calls ‘frugal science,’ designing inexpensive laboratory instruments that can spread science and medical opportunity around the world.”

Thanks to the Explorers program, he’ll gain $10,000 to support his research and a year in the international spotlight. As indicated in the article, expectations of him and the other winners are high:

“Our Emerging Explorers are inspiring young visionaries who are looking at ways to remedy global problems and are undertaking innovative research and exploration,” said Terry Garcia, National Geographic’s chief science and exploration office. “They will help lead a new age of discovery.”

Here’s to looking forward to year of innovative “frugal sciences” creations from the Prakash lab.

Previously: Microscopes for the masses: How a Stanford bioengineer is helping everyone “think like scientists”, Miniature chemistry kit brings science out of the lab and into the classroom or field, Stanford bioengineer among Popular Science magazine’s “Brilliant 10”Manu Prakash on how growing up in India influenced his interests as a Maker and entrepreneur and Stanford bioengineer develops a 50-cent paper microscope
Photo, of Manu Prakash and a group of children in Nigeria, courtesy of Prakash

Bioengineering, Microbiology, Research, Technology

Basic biochemical puzzles that help diagnose and treat disease

Basic biochemical puzzles that help diagnose and treat disease

Welcome to Biomed Bites, a weekly feature that introduces readers to some of Stanford’s most innovative researchers. 

Pehr Harbury, PhD, has made a career out of solving biochemical puzzles. An associate professor of biochemistry, Harbury and his team are juggling quite a few challenges, including an effort to assemble a library of small molecules. Here’s Harbury in the video above:

One central area has been to develop techniques to perform the directed evolution of small molecules in much the same way that nature has produced the vast collection of natural products that are central to medicine.

Team members then examine the molecules to search for ones that interact with natural compounds, potentially conferring beneficial properties.

Harbury is also working to understand the shapes that proteins make when they’re in solution – “a problem that remains largely unsolved.” He describes several other projects – some which he said could lead to an earlier diagnosis for pulmonary hypertension or cancer – in the video above.

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

Previously: Getting a glimpse of the shape molecules actually take in the cell, New painkiller could tackle pain, without risk of addiction and Another piece of the pulmonary-hypertension puzzle gets plugged into place

Bioengineering, Cardiovascular Medicine, Stanford News, Surgery, Technology

A jugaad for keeping pacemakers in place

A jugaad for keeping pacemakers in place

This post is part of the Biodesign’s Jugaad series following a group of Stanford Biodesign fellows from India. (Jugaad is a Hindi word that means an inexpensive, innovative solution.) The fellows will spend months immersed in the interdisciplinary environment of Stanford Bio-X, learning the Biodesign process of researching clinical needs and prototyping a medical device. The Biodesign program is now in its 14th year, and past fellows have successfully launched 36 companies focused on developing devices for unmet medical needs.

IMG_6308After months of observing clinics and winnowing down the most pressing (and commercially viable) medical needs, the Stanford-India Biodesign team has developed what looks like nothing so much as a very elaborate clothespin. It is intended to help doctors ensure that coiled pacemaker leads that screw into heart tissue stay put. Currently, about five percent of those leads fall out, requiring costly additional surgery. Worldwide, the number of people whose leads fall out is estimated at 80,000 to 100,000.

Debayan Saha says their prototype is a perfect example of Indian Jugaad. It’s made of what looks like the contents of a scrap pile, and he says could both work and be cheap to produce in it’s current low-tech form. But just because it’s inexpensive doesn’t mean it’s not cleverly designed. That’s what the Indian team brings to Biodesign, he said – smart technology at low cost.

“Getting the prototype exactly right made use of all the resources we have here at Stanford,” Saha said. “But the final product is something we could produce at very low cost.” Creating technology in a developing country requires creative solutions to keep that technology affordable.

IMG_6326The group has a provisional patent on their device and they will present their it to the entire biodesign team June 8. Until that presentation they are keeping it’s exact function under wraps. They did recently test the prototype in a lamb heart, with good results. They were consistently able to screw the pacemaker lead more securely into the heart tissue.

Harsh Sheth, MD, said the team (which also includes Shashi Ranjan, PhD) will be heading back to India at the end of June and will repeat the same process there – visiting clinics, assessing needs, and prototyping a solution. He said they might later return to their Stanford prototype or keep working on whatever they design in India.

Previously: From popsicle sticks to improved medical careThe next challenge for biodesign: constraining health-care costs and Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India
Photos, of Debayan Saha screwing a pacemaker lead into a lamb heart using their prototype, and of the coiled screw going into the heart, courtesy of Amy Adams

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