Published by
Stanford Medicine

Category

Applied Biotechnology

Applied Biotechnology, Ask Stanford Med, Clinical Trials, Research, Stanford News

SPARKing a global movement

SPARKing a global movement

browser-98386_1280

Many academic researchers are tenacious, spending years in the lab studying the processes that lead to human diseases in hopes of developing treatments. But they often underestimate how difficult it is to translate their successful discovery into a drug that will be used in the clinic.

That’s why Daria Mochly-Rosen, PhD, founded SPARK, a hands-on training program that helps scientists move their discoveries from bench to bedside. SPARK depends on a unique partnership between university and industry experts and executives to provide the necessary education and mentorship to researchers in academia.

In recent years, Stanford’s program has sparked identical programs throughout the world; at TEDMED 2015, Mochly-Rosen described this globalization. I recently spoke with her about the SPARK Global program, which she co-directs with Kevin Grimes, MD, MBA.

How has SPARK inspired similar programs throughout the world?

We’ve found our solution for translational research to be particularly powerful. Of the 73 completed projects at Stanford, 60 percent entered clinical trials and/or were licensed by a company. That’s a very high accumulative success rate. So I think it has showed other groups that we have a formula that really works – a true partnership with academia and industry. It’s the combination of industry people coming every week to advise us and share lessons learned and our out-of-the-box, risk-taking academic ideas that makes SPARK so successful.

We feel that what we’ve learned is applicable to others. Kevin and I also feel very strongly that universities need to take responsibility to make sure inventions are benefitting patients. So we’re trying to do our part.

How do you and Dr. Grimes help develop the global programs?

When a university asks about our program, we invite them to come visit us for a couple of days so they can talk to SPARKees (SPARK participants), meet SPARK advisors and watch our weekly meeting. Sometimes they also ask Kevin and I to come to their country to help set up a big event or assist in other ways. If they begin a translational research program at their institution, we offer for them to be affiliated with SPARK Global. Everyone is invited.

There are now SPARK programs throughout the world, including the United States, Taiwan, Japan, Singapore, South Korea, Australia, Germany and Brazil. We are also working with other countries, including Norway, Israel, Netherlands, Poland and Finland, to help them start a program.

Do researchers in other countries face the same challenges as those in the U.S. when developing new drugs?

There are many common challenges. And there are also some advantages and challenges that are different in other places. So it’s a mix, both within and outside the U.S.

There are several key components to the success of translation research. It’s important to have a good idea. It’s even more important to have good advisors from industry to help develop the idea. And it’s very important that the people involved are open-minded and not inhibited by hierarchical structures. In some places, there is a big problem with hierarchy – particularly in parts of Europe and East Asia. In some cultures, it’s also difficult to get experts to volunteer and academics can’t afford to pay multiple advisors. Also, some universities don’t have a good office of technology to help with patent licensing, which can be a major challenge.

Continue Reading »

Applied Biotechnology, Ethics, Medicine and Society, Public Safety, Science Policy, Stanford News

Stanford experts slam government’s myopic biosecurity oversight

Stanford experts slam government's myopic biosecurity oversight

blindfoldedJust because we can, does that mean we should?

In a hard-hitting editorial in Science, three Stanford thinkers – Stanford microbe wizard David Relman, MD; synthetic biologist Megan Palmer, PhD, of Stanford’s Center for International Security and Cooperation; and political theorist Francis Fukuyama, PhD, of the Freeman Spogli Institute for International Studies – have issued a scathing wake-up call to the scientific community and the federal government, sternly questioning the latter’s current plans for ensuring biosafety and biosecurity in the United States.

“Our strategies and institutions for managing biological risk in emerging technologies have not matured much in the last 40 years,” they write, adding:

With the advent of recombinant-DNA technology, scientific leaders resorted to halting research when confronted with uncertainty and public alarm about the risks of their work. To determine a framework for managing risk, they gathered at the now-fabled 1975 Asilomar meeting. Their conclusions led to the recombinant DNA guidelines still used today, and Asilomar is often invoked as a successful model for scientific self-governance.

But, the authors suggest, Asilomar’s legacy may not be all it’s cracked up to be:

Asilomar created risky expectations: that leading biological scientists are best suited for and wholly capable of designing their own systems of governance and that emerging issues can be treated as primarily technical matters.

“Unfortunately,” the editorial goes on to say, “today’s leadership on biological risk reflects Asilomar’s risky legacy: prioritizing scientific and technical expertise over expertise in governance, risk management, and organizational behavior.” Political leaders have largely ceded a strategic leadership role, leaving it up to the scientific community itself to judge the ethical and social implications of its own work.

“Leadership biased toward those that conduct the work in question can promote a culture dismissive of outside criticism and embolden a culture of invincibility” regarding emerging biotechnology risks,” the authors write.

The world of today is not the world of 1975. Since then, the scope and scale of biological science and technology have changed radically. To wit: The increased ease of reading and writing genetic information means that securing materials in a handful of established labs is not feasible, the editorial states. Like it or not, the tools for putting potentially dangerous knowledge into practice are increasingly portable.

For a scary scenario of what such new facility portends, please see this article I wrote a couple of years ago, which begins with the rhetorical question: “What if nuclear bombs could reproduce?”

With so much at stake, we may not want to restrict oversight of scientific advances to those who are making the advances. There’s knowledge, and there’s wisdom.

Previously: How-to manual for making bioweapons found on captured Islamic State computer, Microbial mushroom cloud: How real is the threat of bioterrorism? (Very) and Stanford bioterrorism expert comments on new review of anthrax case
Photo by Mirko Tobias Schafer

Applied Biotechnology, Bioengineering, Stanford News, Videos

Manu under the microscope

Manu under the microscope

Warning: This video could change the way you look at the world.

So if you’re willing, take the deep dive into this New Yorker magazine video and story, which capture the curiosity-driven magic of Stanford bioengineering inventor Manu Prakash, PhD, and his low-cost microscope, called the Foldscope.

This deceptively simple invention is a bookmark-looking assembly made of folded cardstock, a tiny glass bead and a photo battery, that can take you on a fantastic voyage into the microcosmos.

Last year Prakash shipped free Foldscopes around the world, and created a cult-like following of people sharing their microscopic discoveries. The New Yorker article goes on to describe some of the ways that people are using this invention:

The Foldscope performs most of the functions of a high-school lab microscope, but its parts cost less than a dollar. Last year, with a grant from Gordon Moore’s philanthropic foundation (Moore co-founded Intel), Prakash and some of his graduate students launched an experiment in mass microscopy, mailing fifty thousand free Foldscopes to people in more than a hundred and thirty countries, who had volunteered to test the devices. At the same time, they created Foldscope Explore, a Web site where recipients of the kits can share photos, videos, and commentary. A plant pathologist in Rwanda uses the Foldscope to study fungi afflicting banana crops. Maasai children in Tanzania examine bovine dung for parasites. An entomologist in the Peruvian Amazon has happened upon an unidentified species of mite. One man catalogues pollen; another tracks his dog’s menstrual cycle.

If you’d like to explore with your own Foldscope, you’ll have to be patient. Prakash is still in the planning process of manufacturing and distribution. In the meantime, you can put your name on the round-two waiting list at foldingmicroscope@gmail.com.

Previously: Foldscope beta testers share the wonders of the microcosmosStanford microscope inventor invited to first White House Maker Faire, The pied piper of cool science tools and Stanford bioengineer develops a 50-cent paper microscope
Video by Sky Dylan-Robbins

Applied Biotechnology, Events, Genetics, Research, Stanford News, Technology

Stanford Genome Technology Center retreat highlights interdepartmental synergy

Stanford Genome Technology Center retreat highlights interdepartmental synergy

IMG_0108The recent Stanford Genome Technology Center retreat drove home for me why it’s a great idea to put biochemists, geneticists, engineers, and physicians in a lab together.

Set up in 1989 to establish automated methods for the Human Genome Project, SGTC works to increase the speed, accuracy, and cost-effectiveness of genomic, biomedical, and diagnostic technologies. The center integrates personnel from Stanford’s departments of genetics, biochemistry, medicine, and electrical engineering. At the two-day retreat, researchers presented their latest work in areas like synthetic biology, genome sequencing applications, single-cell approaches, and devices for cellular and molecular detection.

Since I joined SGTC this summer, I’ve gotten a firsthand view of the benefits of combining engineers and biologists. As our engineer Rahim Esfandyarpour, PhD, told me, “We have a lot of solutions – you biologists just need to tell us what the problems are.” The solutions presented at the retreat ranged from ‘sequencing by seeing’ – literally reading DNA molecules under an electron microscope – to a nanopipetting technology that noninvasively takes tiny samples from individual cells, to electrical ‘needles’ that can detect interactions between individual cells or even molecules, to wearable devices that quantify molecules in sweat.

Continue Reading »

Applied Biotechnology, Bioengineering, Stanford News, Technology

The rocket men and their breathtaking invention

The rocket men and their breathtaking invention

rocket_men_560

It’s a gadget straight out of Star Trek — a breath analyzer that may someday quickly and noninvasively detect everything from diabetes to cancers.

In a new Stanford Medicine magazine story, you can read about how three Stanford rocket-combustion experts — Christopher Strand, Victor Miller and Mitchell Spearrin — designed and tested a Breathalyzer-like device to measure toxic ammonia levels in critically ill children, all in about a year.

Breath testing with the human nose has been used in medicine since ancient times. (The rotten-apple smell of acetone is a sign of diabetes. A fishy smell is indicative of liver disease.) The rocket men in the story recognized the opportunity to develop a medical device that could transform this art into a science.

They figured that the technology they used in rocket testing, laser absorption spectroscopy, would be sensitive enough to make measurements of trace compounds in the breath. Just as engineers can use these data to tell if a rocket engine is operating efficiently, they could tell if a human biochemical engine is operating in a healthy range. Their project mentor, Gregory Enns, MD, a biochemical geneticist who diagnoses and treats metabolic diseases at Lucile Packard Children’s Hospital Stanford, helped the team get up to speed on metabolic disorders and remove bureaucratic roadblocks to clinical testing.

What was most inspiring to me about this story was the indefatigable optimism of the engineering team. The rocket men chose the most difficult molecule to measure (ammonia), a disease caused by a rare genetic defect with little commercial potential (hyperammonemia), and a hard-to-test patient population (infants). During the development process, they demonstrated the same mental toughness as abandoned-on-Mars engineer Mark Watney in the film “The Martian“; as each insurmountable technical challenge came up, they did what Watney did: “science the hell out of it.”

Previously: Stanford physicians and engineers showcase innovative health-care solutionsRaising awareness about rare diseases, Extraordinary Measures: a film about metabolic disease
Photo by Misha Gravenor

Applied Biotechnology, Big data, Cancer, Genetics, Research, Science, Stanford News

Peeking into the genome of a deadly cancer pinpoints possible new treatment

Peeking into the genome of a deadly cancer pinpoints possible new treatment

small cell lung cancerSmall cell lung cancer is one of the most deadly kinds of cancers. Typically this aggressive disease is diagnosed fairly late in its course, and the survival rates are so dismal that doctors are reluctant to even subject the patient to surgery to remove the tumor for study. As a result, little is known about the molecular causes of this type of cancer, and no new treatments have been approved by the Food and Drug Administration since 1995.

Now a massive collaboration among researchers around the world, including the University of Cologne in Germany and Stanford, has resulted in the collection of more than 100 human small cell lung cancer tumors. Researchers sequenced the genomes of the tumors and identified some key steps in their development. They also found a potential new weak link for treatment.

The findings were published today in Nature, and Stanford cancer researcher Julien Sage, PhD, one of three co-senior authors of the paper, provided some details in an email:

With this larger number of specimens analyzed, a more detailed picture of the mutations that contribute to the development of small cell lung cancer now emerges. These studies confirmed what was suspected before, that loss of function of the two tumor suppressor genes, Rb and p53, is required for tumor initiation. Importantly, these analyses also identified new therapeutic targets.

The researchers also saw that, in about 25 percent of cases, the Notch protein receptor was also mutated. This protein sits on the surface of a cell; when Notch binds, it initiates a cascade of signaling events within the cell to control its development and growth. As Sage explained:

The mutations in the Notch recepetor were indicative of loss of function, suggesting that Notch normally suppresses small cell lung cancer development. Indeed, when graduate student Jing Lim in my lab activated Notch in mice genetically engineered to develop small cell lung cancer, we found a potent suppression of tumor development. These data identify the Notch signaling pathway as a novel therapeutic target in a cancer type for which new therapies are critically needed.

This is not Sage’s first foray into fighting small cell lung cancer. In 2013, he collaborated with other researchers at Stanford, including oncologist Joel Neal, MD, PhD, to identify a class of antidepressants as a possible therapy for the disease.

Previously: Gene-sequencing rare tumors – and what it means for cancer research and treatment, Listening in on the Ras pathway identifies new target for cancer therapy and Big data = big finds: Clinical trial for deadly lung cancer launched by Stanford study
Image by Yale Rosen

Applied Biotechnology, In the News, Research, Stem Cells, Transplants

“Supplying each cell with a scuba tank”: New advances in tissue engineering

"Supplying each cell with a scuba tank": New advances in tissue engineering

membrane-article.jpgResearchers in the U.K. have found a way to make growing synthetic tissue more sustainable. At present, the size of engineered tissues is limited because the cells die from lack of oxygen when the pieces get too big. By adding an oxygen-carrying protein to the stem cells prior to combining them with tissue scaffolding, the researchers overcame this problem.

The study, led by Adam Perriman, PhD, research fellow at the University of Bristol’s Synthetic Biology Research Centre, and Anthony Hollander, PhD, professor of integrative biology at the University of Liverpool, was published yesterday in Nature Communications. The tissue they were fabricating was cartilage, but the process could potentially be applied to other tissues, as well.

Perriman describes the findings in a press release:

We were surprised and delighted to discover that we could deliver the necessary quantity [of oxygen] to the cells to supplement their oxygen requirements. It’s like supplying each cell with its own scuba tank, which it can use to breathe from when there is not enough oxygen in the local environment.

Hollander also comments on the significance of the research:

We have already shown that stem cells can help create parts of the body that can be successfully transplanted into patients, but we have now found a way of making their success even better. Growing large organs remains a huge challenge but with this technology we have overcome one of the major hurdles.

Creating larger pieces of cartilage gives us a possible way of repairing some of the worst damage to human joint tissue, such as the debilitating changes seen in hip or knee osteoarthritis or the severe injuries caused by major trauma, for example in road traffic accidents or war injuries.

Previously: Building bodies, one organ at a time, How Stanford researchers are engineering materials that mimic those found in our own bodies and A brief look at “caring” for engineered tissue
Photo by Warwick Bromley

AHCJ15, Applied Biotechnology, Imaging, Mental Health, Neuroscience, Technology

Talking about “mouseheimers,” and a call for new neuroscience technologies

Talking about "mouseheimers," and a call for new neuroscience technologies

3723710203_1b8c9d96ed_zOur ability to technologically assess the brain has room for improvement, according to panelists at the recent Association of Health Care Journalism 2015 conference. Amit Etkin, PhD, MD, a neuropsychiatrist at Stanford, summed it up when he said, “We need to develop tools to answer questions we want to ask, rather than ask questions we can answer with the tools we have.”

Etkin asserted that there have been no fundamental advances in psychiatry since 1987; all the medications put out now are basically the same, and the treatments work partially, sometimes, and for only some people. Interdisciplinary work combining psychiatry, neuroscience, and radiology is the frontier: Researchers are just getting a sense of how “interventional neuroscience,” such as that pioneered at the interdisciplinary NeuroCircuit initiative at the Stanford Neurosciences Institute, can identify which brain regions control various processes. This involves looking at brain signatures that are common across disorders, instead of dividing and parsing symptoms, which is the approach of the Diagnostic and Statistical Manual of Mental Disorders.

Researchers are searching for an ideal marker for Alzheimer’s: something predictive (will you get the disease?), diagnostic (do you have the disease?), and dynamic (how severe is your disease right now?)

Michael Greicius, MD, MPH, professor of neurology and neurological sciences at Stanford, researches Alzheimer’s and has a bone to pick with media hype about Alzheimer’s research conducted in mice. What the mice have shouldn’t be considered the same condition, he says, so he’s termed it “mouseheimer’s.” Only 2 percent of the Alzheimer’s population has the dominant, inherited, exceedingly potent genetic form, which is the form used in research on rodents. Further, the mice are double or even triple transgenic. We still use these improbable biological hosts because we need an artificial model: Alzheimer’s is really just a human thing, and even great apes don’t get it. The next best modeling possibility, he suggested, are flies.

Continue Reading »

Applied Biotechnology, Bioengineering, Research, Science, Technology

New retinal implant could restore sight

New retinal implant could restore sight

2618400441_c19946dff4_zIf your car battery runs out of juice, the car won’t run, but that doesn’t mean it’s time to scrap the car. Similarly (at least slightly), if your photoreceptors are worn out due to a disease such as retinitis pigmentosa or macular degeneration, then you might not be able to see, but your eyes still have a lot of functioning parts.

That’s the principle behind a new retinal implant developed by team of Stanford-led researchers. Unlike previous devices, which require wires and unwieldy surgeries, the new implant is wireless and needs only a minimally invasive surgery to inject a small, photovoltaic chip inside the eye. The team published their results in Nature Medicine.

That chip capitalizes on the remaining capabilities of existing retinal cells known as bipolar and ganglion cells and produces more refined images than existing devices. The chip responds to signals from special glasses worn by the recipient.

“The performance we’re observing at the moment is very encouraging,” Georges Goetz, a lead author of the paper and graduate student in electrical engineering at Stanford, said in our press release. “Based on our current results, we hope that human recipients of this implant will be able to recognize objects and move about.”

The implant has only been used in animal studies, but a clinical trial is planned next year in France.

“Eventually, we hope this technology will restore vision of 20/120,” co-senior author Daniel Palanker, PhD, told me. “And if it works that well, it will become relevant to patients with age-related macular degeneration.”

Previously: Stanford researchers develop solar powered wireless retinal implant, Factors driving prescription decisions for macular degeneration complex — and costly and Tiny size, big impact: Ultrasound powers miniature medical implant 
Photo by Ali T

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

An inside look at drug development

An inside look at drug development

B0008664 Assorted pills, tablets and capsules

How are drugs born? If you’re really curious about this, you’d be fascinated by the weekly meetings of industry experts and academic researchers taking part in Stanford’s drug-development training program known as SPARK.

A recently published book, A Practical Guide to Drug Development in Academia, crystallizes the sessions. Even if you’re not a scientist dreaming of curing cancer with your latest discovery, you might find it interesting.

In his recent review of the book for Nature Chemical Biology, industrial medicinal chemist Derek Lowe, PhD, writes:

I would actually welcome it if this book’s intended audience were broadened even more. Younger scientists starting out in the drug industry would benefit from reading it and getting some early exposure to parts of the process that they’ll eventually have to understand. Journalists covering the industry (especially the small startup companies) will find this book a good reality check for many an over-hopeful press release. Even advanced investors who might want to know what really happens in the labs will find information here that might otherwise be difficult to track down in such a concentrated form.

Lowe also wrote about the book last week on his blog, In the Pipeline, where an interesting discussion has begun.

Previously: SPARK program helps researchers cross the “valley of death” between drug discovery and development and Accelerating the translation of biomedical research into clinical applications.
Photograph from Wellcome Images

Stanford Medicine Resources: