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Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Following the heart and the mind in biodesign

Following the heart and the mind in biodesign

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.

15125593898_7ee05d0a60_zWhen I showed up to meet with the Biodesign fellows, Debayan Saha greeted me by saying, “We are arguing – please join us.”

The source of the argument turned out to be a thorny one. The team had previously attended cardiovascular disease clinics and from those visits identified more than 300 possible needs that, if addressed, might improve patient care.

Now, their job was to narrow down those 300+ needs to the one they would eventually develop a prototype device to address.

Part of the process Stanford Biodesign fellows learn is a rigorous method for identifying medical needs that also make business sense to address. The first step: eliminate the duds.

In this round, the each team member had individually rated the needs according to their individual levels of interest on a scale of 1 to 4. That interest could reflect the fact that they think the technology is interesting, or the fact that the need is one they would be excited about addressing.

Now they were trying to rate the needs on the same 1 to 4 scale according to the number of people who would benefit if it were addressed. The combination of these two ratings—one subjective and the other objective—would produce a shorter list of needs that were both of interest to the fellows and would benefit enough people that any future company could be successful

That objective rating was the source of the polite disagreement I had walked into. As one example, if a particular need applied to people who had a stroke, should they assume that all people who have had a stroke would benefit from a solution (giving the need a higher rating of 4), or would only a small subset benefit (giving the need a lower rating of 1 or 2)?

By and large Harsh Sheth, MD, leaned toward 4s while Shashi Ranjan, PhD, leaned toward 2s. Saha mostly just leaned back. Much discussion ensued.

In the end the team managed to assign a single score indicating the number of people represented by each need. When combined with their subjective scores, the group was able to eliminate the lowest scoring needs and reduce the list to a mere 133.

One interesting thing I learned is that this careful rubric is harder to apply in India, where good numbers about how many people have particular conditions are harder to come by. Ranjan told me that even in India they would likely use U.S. numbers for some conditions and just scale up to the Indian population. I mentally added this lack of good data to the list of reasons Stanford-India Biodesign Program executive director (U.S.) Rajiv Doshi, MD, told me that biodesign is more challenging in India.

Previously: Writing a “very specific sentence” is critical for good biodesign and Good medical technology starts with patients’ needs
Photo by Yasmeen

Ask Stanford Med, Global Health, Stanford News, Technology

Stanford-India Biodesign co-founder: Our hope is to “inspire others and create a ripple effect” in India

Stanford-India Biodesign co-founder: Our hope is to "inspire others and create a ripple effect" in India

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.

shutterstock_258773231Rajiv Doshi, MD, is the executive director (U.S.) of the Stanford-India Biodesign Program and was part of the Stanford team that initially flew to India in 2007 to propose the program to the Government of India. He has commercialized devices to treat sleep apnea and snoring and later served on boards of multiple medical device companies. In 2012 he was named by Forbes India as one of the top 18 Indian scientists who are changing the world.

Doshi answered questions about the early days of the Stanford-India Biodesign program and the hurdles entrepreneurs face in India.

Why did you want to start the Stanford-India Biodesign program?

Starting the program was both an opportunity and an obligation. My belief was that this was going to be a difficult challenge spanning perhaps a decade. We were working with a partner [the Indian government] where we didn’t know the people very well and we didn’t know many of their systems. We had never assembled such an international collaboration of this scale. If we failed then at least we tried and did our best. If we were successful then we would have helped a lot of people. I felt that this was a once in a lifetime opportunity to have an impact of this scale.

What were some of the hurdles the early fellows faced when they tried to develop technologies in India?

Probably the number one problem they face in India is that there is really little mentorship as we know it here. Few people in India have successfully developed a medical device from scratch so it is really hard to find mentors who are already domain experts in medical technology. The next issue is raising capital. There is very little early stage venture capital focused on medical technology in India.

Then there are challenges with research and development. Imagine you’re creating a difficult-to-make medical device that has small, complicated parts. Odds are the suppliers aren’t available for all these parts in India. Then there’s manufacturing and supply chain issues. Let’s say the entrepreneurs are able to develop a product, then they may struggle to find an in-country manufacturer to make this product. In many cases, in-country manufacturing capabilities just aren’t at the same level as you would see here or in Singapore, Germany or other locations. So you start stacking these challenges together and you realize that they are pretty serious.

Does it get easier once they’ve developed the device?

No, I think the greatest challenges are related to commercialization – after development has been completed. Let’s imagine you created a great product, you’ve figured out all these issues. Your next challenge is then to market your product and convince healthcare providers in India to start using your product. This takes time and money to support your marketing and sales efforts. Additionally, many of the providers may not be as trained as their US or UK counterparts and may be less likely to adopt your product if it requires a certain level of training. Finally, there is the issue of who is going to pay for the product. In India, only about 25 percent of people have basic health insurance so any device in India needs to be quite low cost to be broadly used.

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Neuroscience, Research, Stanford News

A little noise in the brain’s wiring helps us learn

A little noise in the brain's wiring helps us learn

shutterstock_139305437It didn’t come as a surprise to me when I learned from neuroscience postdoctoral scholar Tatiana Engel, PhD, that all of us have a bit of noise in how our neurons fire. In response to the same signal, they’ll usually fire one way then occasionally fire a different way.

I, myself, blame a number of my quirks on noisy and confused neurons.

Engel told me that Stanford Neurosciences Institute director William Newsome, PhD, had discovered those noisy neurons almost two decades ago. He had trained animals to detect whether dots on a screen were moving to the right or left. He found that the way a single noisy neuron fired was also reflected in how the animal categorized the dots – if the neuron indicated right, the animal chose right and vice versa.

In a story I wrote Engel said, “[It]was exciting to me to realize that we are used to thinking about ourselves as agents who are in charge of our decisions and in charge of our thoughts, but the brain might be playing tricks with us.”

Engel recently published work she did in computer models in which she tried to understand why the neurons didn’t fire the same way every time. What she found is that if neurons don’t have a bit of a bias to begin with they don’t learn through a reward system. Essentially without occasionally firing left when the dots are moving right, the neuron can’t ever improve its accuracy.

The type of learning Engel studied is the same kind of learning we use when learning to categorize food into groups we like or don’t like, or to categorize music or even objects. Her work appears in Nature Communications.

Previously: Stanford neurobiologist Bill Newsome: Seeking gains for the brain and Deciphering “three pounds of goo” with Stanford neurobiologist Bill Newsome
Image from Shutterstock

Bioengineering, Cardiovascular Medicine, Stanford News, Technology

Writing a “very specific sentence” is critical for good biodesign

Writing a "very specific sentence" is critical for good biodesign

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.

1 After several weeks spent following doctors through cardiovascular disease clinics, Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD, together identified 315 apparent medical needs ranging from better ways of monitoring patients to improvements of existing devices. During the course of their six-month fellowship, they’ll develop a prototype device to solve just one.

The first step toward picking that one is to better define the 315.

This is more complicated than it seems. For example, one of the needs they’d originally written down involved real-time monitoring of certain molecules in the patient’s blood. They revised that phrasing because it defined the solution – real time – rather than the problem, which is the need for doctors to have more accurate information about the patient’s blood so they can make better treatment decisions. “One solution to the problem might be real-time, but there might be another way,” Sheth said.

Similarly, another need they identified had to do with a device that was inconvenient for doctors to use during a medical procedure. Did they need to improve the device to make a procedure more efficient, or was the need specifically for a smaller device? With another device, they debated whether the real need was to reduce the patient’s pain or to reduce the blood loss.

Some of these decisions might sound like splitting hairs – whether the problem is pain or blood loss, there is a clear need for a better device. But the distinction makes a difference down the road. If they chose to focus on the pain rather than the blood loss, that would effect what insurance will pay for its use and intellectual property – factors that make a difference in whether or not a device can get funding and eventually reach patients.

“We need a very specific sentence to make very clear the need we are trying to solve,” Saha said.

Eventually the team will sort through this list of needs to identify the single focus of the remainder of their time.

One thing I found interesting: In fourteen years of the program, each year with several teams working on the same medical field, no two teams have ever developed devices to satisfy the same need.

Previously: Good medical technology starts with patients’ needs and Biodesign program welcomes last class from India
Photo of Shashi Ranjan and Harsh Sheth on a clinical visit by Kurt Hickman

Bioengineering, Stanford News

Miniature chemistry kit brings science out of the lab and into the classroom or field

Miniature chemistry kit brings science out of the lab and into the classroom or field

KorirA few months ago, Stanford bioengineer Manu Prakash, PhD, and graduate student George Korir were recognized for an ingenious (to me) contraption built from a music box that creates a simple way of doing very small scale chemistry experiments.

That award, from the Gordon and Betty Moore Foundation and the Society for Science & the Public, recognized the device for its possible use as a chemistry set for kids, but Prakash and Korir also see it as useful for scientists in a lab or out in the field.

They’ve now published the device in PLoS ONE , describing its functionality for scientists as well as kids.

The general idea is that this 100 gram device uses a hand crank to wind a long punch card through metal prongs. In its original state, those metal prongs then each played a note on queue. In their reconfiguration, each metal prong releases a droplet of a chemical or controls pumps and valves.

At only two inches in length, Prakash and Korir say the device is easy to carry and could be programmed to carry out chemistry experiments outside the lab – testing water quality or soil samples, for example.

“The platform is simple to use and its plug and play nature makes it accessible to both untrained health workers in the field and young children in classrooms,” Prakash wrote.

This device is part of Prakash’s ongoing focus on frugal science – devices that are inexpensive and functional enough to bring science out of the lab and into the world. He previously developed a 50 cent microscope called the Foldscope that is being used by groups worldwide to investigate their environment. Some of the images taken through the Foldscope can be viewed here.

Previously: Music box inspires a chemistry set for kids and scientists in developing countries and Foldscope beta testers share the wonders of the microcosmos
Photo by Kurt Hickman

Bioengineering, Cardiovascular Medicine, Medical Education, Research, Technology

Good medical technology starts with patients’ needs

Good medical technology starts with patients' needs

biodesign fellows

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.

The first step in solving a medical challenge is identifying a problem in need of a solution. This seems intuitive, but often people start from the other direction – they’ve developed a technology and go looking for some way to apply it.

Learning that workflow is one thing that brought Shashi Ranjan to the Stanford Biodesign program from Singapore. “I was making devices but didn’t see them going into people,” he told me. “I wanted my technology to go into the real world.”

As the fellows encounter patients and doctors, they are compiling a list of existing medical needs.

Ranjan, along with Harsh Sheth, recently visited the Stanford South Asian Translational Heart Initiative run by Rajesh Dash, MD, PhD, to witness first-hand cardiovascular needs encountered by South Asians in the Bay Area. (The third member of their team, Debayan Saha, was at a different clinic that day.) After observing some patients, what became clear to the two is that lifestyle changes are a major barrier to improving cardiovascular disease risk in South Asians, just like in any other population.

Some of the problems they encountered appear obvious: How do you help people get more exercise and maintain a healthy weight? Develop a device to solve that and the team would help many more people than just patients with cardiovascular disease.

The two had also observed that many people who are overweight have sleep apnea, or short pauses in breathing during sleep, which can contribute to heart disease risk. The devices that exist to help sleep apnea look like cumbersome gas masks and aren’t conducive to a restful slumber. Several patients they observed don’t use the device regularly despite knowing that it could lower their risk of having a heart attack.

After observing patients, the pair added to their growing list of 300 plus medical needs a better air mask for sleep apnea, along with simplified screening for people who are at risk of heart disease. Patients at Dash’s clinic are asked to make routine visits for specialized bloodwork and other screenings. “Can we make the tests simpler but still effective, and available at the point of care?” Sheth asked.

I asked Dash why he wanted to work with Biodesign fellows like Ranjan and Sheth – their presence in the office visit certainly made the room tight and patients perhaps a tad uncomfortable. He told me that training people to make better medical devices is critical to providing good care.

The fellows from India are particularly valuable he said. “They learn how we are approaching the problem here then help find solutions that are effective in India.”

Over the next few weeks, the team will stop visiting clinics and will begin the arduous task of narrowing down their list of more than 300 observed medical needs to the one that will become the focus of their fellowship. (Four other teams are going through a similar process, and they’ll all present their prototypes at a symposium in June.)

Previously: One person’s normal = another person’s heart attack? and Biodesign program welcomes last class from India
Photo, of Shashi Ranjan and Harsh Sheth observing as Rajesh Dash, MD, meets with a patient, by Kurt Hickman

Cardiovascular Medicine, Patient Care

One person’s normal = another person’s heart attack?

One person's normal = another person's heart attack?

Much has been written about calculating your BMI (or body mass index, the relationship between your height to your weight) and what it might indicate about your health.

Similarly, the glucose level in your bloodstream and what it says about your risk of diabetes.

What you don’t hear much about, and what I learned yesterday, is how much the meaning of those numbers can vary between people. A healthy BMI for one person might put another person at risk for heart disease.

I was visiting the Stanford South Asian Translational Heart Initiative run by Rajesh Dash, MD, PhD, along with some Biodesign fellows I’ve been following (more about that in a later post). By way of background on the clinic, Dash explained the high risk of heart disease in the South Asian population. (My colleague Becky Bach blogged about that risk last year.)

Dash said one challenge in helping South Asians avoid heart disease comes from the definitions of “overwieight” and “diabetic”. Dash said that South Asians tend to have more fat per body weight, and so might have an acceptable BMI but still have an amount of fat that puts them at risk for heart disease. Similarly, a South Asian person who is pre-diabetic might benefit from diabetes medication.

“We see a lot of glucose levels that are technically normal but still troubling,” he told me. “Their risk of a cardiovascular event is almost as high as for someone who has diabetes.”

For a population that has four times more heart attacks in California than other ethnic groups, it seemed especially troubling that a mere definition might be preventing them from getting appropriate care.

That got me wondering how those numbers apply to other populations. Or to me.

I had my yearly blood work done recently and was pleased to see that everything was “normal”. I’m curious if in a decade people like Dash and others might have collected enough data to sway the way our values get reported. A set of numbers that is normal for my gender and ethnicity might trigger additional screening in another person, or be considered better than normal for someone else.

Previously: A ssathi (partner) to thwart heart disease in South Asians and Biodesign program welcomes last class from India

Bioengineering, Stanford News

Biodesign program welcomes last class from India

Biodesign program welcomes last class from India

Clark CenterIn January, three fellows from India arrived to Stanford to join the Biodesign program, which immerses clinicians, scientists, engineers and business people in the biodesign process for innovating successful medical devices.

What makes these three unique is that they’re the last class from the Stanford-India Biodesign program to visit home base, housed within the Clark Center and the interdisciplinary environment of Stanford Bio-X. The Indian program has been so successful that after this year they will become independent.

I’ll be following this final group of Indian fellows on their whirlwind tour of clinics, prototyping demos, brainstorming sessions, and courses on intellectual property and regulatory steps as they develop and prototype a medical device – and blogging about them along the way.

The three fellows I’ll be following – Debayan Saha, Shashi Ranjan, PhD, and Harsh Sheth, MD – all say they were drawn to the program in part because of its unique approach. Commonly, people develop medical devices and then look for a problem to apply it to. Or, they come up with a prototype that meets a real need, but don’t research the intellectual property or costs in advance and fail because of that oversight.

In the end, real needs are unmet.

In the Biodesign program, fellows first observe clinicians to learn what the needs are. Then they research the intellectual property, medical costs of the disease, and regulatory hurdles they would have to overcome before they ever start prototyping.

The end result has been 36 start-up companies and international programs in India, Singapore and Ireland all trying to replicate the process and meet their country’s own unique medical needs.

By June, Saha, Ranjan and Sheth will have developed a device prototype that solves a medical need in cardiovascular medicine, and that could potentially get to market. Sheth brings clinical expertise – he is a surgeon – while Ranjan and Saha both have engineering backgrounds.

So far, the group says their clinical visits have resulted in a list of more than 300 needs, which they say will grow before it shrinks down to the final one they decide to address. I’ll be documenting the process of whittling 300+ needs down to a single prototype, and interviewing leaders in Biodesign along the way.

For my next installment: The fellows visit a south Asian cardiovascular disease clinic run by Rajesh Dash, MD, PhD, and wonder if a device can change patient attitudes.

Previously: Biodesign fellows take on night terrors in children, Stanford Biodesign Program releases video series on the FDA system and A medical invention that brings tears to your eyes
Photo of the Clark Center by L.A. Cicero

Cancer, Research, Stanford News

The medical benefits of a little chemistry know-how

The medical benefits of a little chemistry know-how

molecules and beakers

I’ve been writing about medical science for close to 20 years now, and in that time I shudder to think how often I’ve written stories about basic science discoveries that could result in potential future drugs.

I wasn’t exaggerating in those stories. The scientists I had the pleasure of working with really were hopeful about the potential of treating patients. But developing a drug is a long and arduous process and not all discoveries lend themselves to drugs.

As I wrote in a story today:

The chemical in the pill we swallow has to survive the burbling acidic soup of our stomachs and the digestive enzymes capable of reducing steak and potatoes into tiny particles. Once in our bloodstream, a potential drug has to endure the liver’s attempts to detoxify it, and then reach the cell in question and – the hardest part – actually work.

Overcoming those obstacles and turning that discovery into a drug requires medicinal chemistry know-how as well as a detailed knowledge of the drug development and approval process, which aren’t skills in the toolbox of most biologists.

In today’s story, which describes a discovery in pancreatic cancer cells by gastroenterologist Anson Lowe, MD, that could result in a new drug for several different types of cancers, I also got to write about a new medicinal chemistry program started by Stanford ChEM-H.

ChEM-H is a relatively new interdisciplinary institute with a focus on bringing chemistry expertise to issues in human health. With their new medicinal chemistry program, the institute is hoping they can help people like Lowe fulfill the promise that I’ve written about in so many stories – that of turning a discovery into a drug that helps people.

Previously: Stanford ChEM-H bridges chemistry, engineering and medicine, Listening in on the Ras pathway identifies new target for cancer therapy, and New clues arise in pancreatic cancer from Stanford researchers
Photo from Shutterstock

Aging, Neuroscience, Stanford News, Stroke, Videos

Bio-X undergraduate student finds direction through research

Bio-X undergraduate student finds direction through research

Richie Sapp arrived to Stanford as an undergraduate already interested in studying neuroscience. After talking with several faculty members, he ended up working in the lab of Carla Shatz, PhD, director of Stanford Bio-X.

I interviewed Sapp recently for a series of stories I was working on about undergraduate research opportunities at Stanford. He had participated in a terrific summer program run by Bio-X. I was struck by a few things when we talked, one of which was Sapp’s sincere interest in helping people. He had grown up with a twin brother who had been born with hydrocephaly and as a result had learning delays and is on the autism spectrum. That experience shaped his interest in helping people with similar challenges.

Sapp said that through his experience in the lab he got more out of his undergraduate classes and learned a lot about where he wants to go with his life. He loves the research and discovery, but also wants to go the medical school before pursuing research. Without the experience provided by the Bio-X summer program he might not have known which direction to go.

“The experience of designing experiments and seeing a project through to the end is going to be important for me in whatever I do next,” he said.

Here is the full profile about Sapp, with more about his research experiences.

Previously: Drug helps old brains learn new tricks, and heal

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