Disruptive #7: FISSEQ – Fluorescent In Situ Sequencing

Written on October 7th, 2016

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Until recently, to analyze many mRNAs simultaneously, scientists had to grind cells to a pulp, which left them unable to pinpoint those mRNAs within the cell. Developed by a team at the Wyss and Harvard Medical School, FISSEQ allows scientists to pinpoint thousands of mRNAs and other types of RNAs at once in intact cells, and stands to revolutionize clinical diagnostics and drug discovery.

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Disruptive #7 Transcript

Disruptive Episode #7 – FISSEQ – Fluorescent In Situ Sequencing

Written on October 5th, 2016

DISRUPTIVE #7: FISSEQ – Fluorescent In Situ RNA Sequencing
Hello, I’m Terrence McNally and you’re listening to DISRUPTIVE the podcast from Harvard’s Wyss Institute for Biologically Inspired Engineering. 

One of today’s guests, George Church, has made the point that as medicine moves from very blunt instruments – where you had to open up a chest all the way, for example, or had to use molecules that would hit almost every part of your body – now molecules can find one base pair out of six billion and change it – He says we need observational tools that can deal with that high level of resolution and comprehensiveness.

And we’re going to talk about one such tool. Fluorescent in situ RNA sequencing – F-I-S-S-E-Q – or FISSEQ.

Working copies of active genes — called messenger RNAs or mRNAs — are strategically positioned throughout living tissues, and their location often helps regulate how cells and tissues grow and develop. Until recently, to analyze many mRNAs simultaneously, scientists had to grind cells to a pulp, which left them unable to pinpoint where those mRNAs actually sat within the cell.

Now a team at the Wyss Institute and Harvard Medical School has developed a new method that allows scientists to pinpoint thousands of mRNAs and other types of RNAs at once – in intact cells.

FISSEQ could lead to earlier cancer diagnosis, help biologists better understand embryonic development, and even help map the neurons of the brain.

I’ll talk with George Church, Wyss Core Faculty member and co-founder of ReadCoor, the startup that will bring FISSEQ to market; Wyss lead senior scientist, Rich Terry, President, Co-Founder, and CTO of ReadCoor; and Shawn Marcell, Wyss Entrepreneur-in-Residence and founding Chairman/CEO of ReadCoor.

The mission of the Wyss Institute is to: Transform healthcare, industry, and the environment by emulating the way nature builds.

Our bodies — and all living systems — accomplish tasks far more sophisticated and dynamic than any entity yet designed by humans. 

By emulating nature’s principles for self-organizing and self-regulating, Wyss researchers develop innovative engineering solutions for healthcare, energy, architecture, robotics, and manufacturing.
[02:06]

George Church is Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. He’s Director of the U.S. Department of Energy Center on Bioenergy at Harvard and MIT and director of the NIH Center for Excellence in Genomic Science at Harvard. He has co-founded a number of companies, including ReadCoor.

Church earned a bachelor’s degree from Duke University in two years and a PhD from Harvard. Honors include election to the National Academy of Sciences and the National Academy of Engineering. He has coauthored hundreds of scientific papers, more than sixty patents, and the book, “Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves.”  [02:41]

To set the context for this episode, George Church offers an overview of the evolution of sequencing technology –

Church:       It dates back at least to the ’60s when RNA sequencing and protein sequencing were the main ways of getting insight. In the mid-’70s, ways to do DNA sequencing based on electrophoresis came into play. Those were automated and made less radioactive, more fluorescent. In the ’80s and ’90s, it switched from slab electrophoresis, capillary electrophoresis. None of these scaled particularly well.

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Disruptive#6: Rapid, Low-cost, Paper-based Test for Zika

Written on June 24th, 2016

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McNally:
Hello, I’m Terrence McNally and you’re listening to Disruptive, the podcast from Harvard’s Wyss Institute for biologically inspired engineering. In early May, a low cost, rapid, paper-based diagnostic system for strain specific detection of the Zika virus was introduced by an international consortium of researchers led by synthetic biologist James Collins with the goal that it could soon be used in the field to screen blood, urine or saliva samples.

The core of the test kit is a piece of paper that changes color in the presence of Zika virus RNA and produces results in two to three hours. Much faster and cheaper than the PCR test used now according to Collins, a Wyss core faculty member – and it should cost less than a dollar per test adds University of Toronto biochemist Keith Pardee.

I’m going to speak with both of them about the real time story of a crisis
inciting innovation. How a team from a number of different institutions came together, and in a matter of six weeks developed a new approach to detection and designed a system to deploy in the face of future pandemics. Collins says, in response to an emerging outbreak, a custom tailored diagnostic system could be ready for use within one week’s time. We’ll explore how they did it, what they’ve learned and what this might mean for the future.

The mission of the Wyss Institute is to transform healthcare industry and the environment by emulating the way nature builds. Our bodies and all living systems accomplish tasks far more sophisticated and dynamic than any entity yet designed by humans. By emulating nature’s principles for self organizing and self regulating, Wyss researchers develop innovative engineering solutions for healthcare, energy, architecture, robotics and manufacturing.

In addition to leading the Living Cellular Devices and cellular devices platform at the Wyss, Jim Collins is the Termeer professor of medical engineering and science and professor of biological engineering at MIT. He’s a member of the Harvard MIT health sciences and technology faculty and an institute member of the Broad Instiute of MIT and Harvard.

Collins received a BA in physics from Holy Cross and a PHD in medical engineering from Oxford. A Rhodes Scholar, a MacArthur Fellow and a winner of the National Institutes of Health Directors Pioneer Award. Jim is one of the founders of synthetic biology as well as a pioneering researcher in systems biology and his engineering ranges from the physical scale of wearable medical devices to that of molecules.

Collins says he found early inspiration both in the space program and much closer to home.

Collins: [02:38]
I was born and grew up initially in New York City. My dad was an electrical engineer who had worked in the aviation industry so he did work for NASA, he did work for the military, he did work for a number of companies building planes. My mom was a math teacher.

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Q&A: ATUL GAWANDE – Surgeon / Teacher / Author – The Checklist Manifesto

Written on January 8th, 2015
  Aired 03/14/10 Though Atul Gawande is a best-selling author, a Harvard professor, and an innovator in best practices for the W.H.O., he still performs 250-plus surgeries a year. A framed copy of Sylvia Plath's poem "The Surgeon at 2 a.m." stands on the desk in his office." Her surgeon's words: "I worm and hack in a purple wilderness." Gawande likes the Plath poem because it casts the surgeon in an ambiguous light. "Most writing about people in medicine casts them as either heroes or villains," he says, "That poem captures the surgeon as a merely human, slightly bewildered and benighted person in a world that is ultimately beyond his control."
Medicine is just one area of our world that is becoming so complex that even the most expert professionals struggle to master the tasks they face. In his new book, The Checklist Manifesto, Gawande offers a disarmingly simple remedy: the checklist. Now being adopted in hospitals, the 90 second practice cuts fatalities In surgery by more than a third. NOTE: This interview was recorded when Gawande was recently in LA, prior to Obama's healthcare summit and the latest legislative negotiations. http://gawande.com/

Q&A: DAVID GOLDHILL, AUTHOR- CATASTROPHIC CARE: How American Health Care Killed My Father And How We Can Fix It

Written on October 31st, 2014
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Aired: 02/03/13

This week, my guest is DAVID GOLDHILL. After the death of his father, Goldhill, a business executive, began a personal exploration of a health-care industry that for years has delivered poor service and irregular quality at astonishingly high cost.

His September 2009 Atlantic cover story rocked the health-care world, and Goldhill has written a book expanding on the topic, Catastrophic Care: How American Health Care Killed My Father-And How We Can Fix It. It is a system, he argues, that is not worth preserving in anything like its current form. He asserts Obamacare will not fix it, and offers his own radical solution.

* As a nation, we now spend almost 18% of our GDP on health care.

* In 1966, Medicare and Medicaid made up 1% of total government spending; now that figure is 20%.

* The federal government spends
– 8 times as much on health care as it does on education
— 12 times what it spends on food aid to children and families
— 30 times what it spends on law enforcement
— 78 times what it spends on land management and conservation
— 87 times the spending on water supply
— 830 times the spending on energy conservation.

* For every two doctors in the U.S., there is now one health-insurance employee-more than 470,000 in total. In 2006, it cost almost $500 per person just to administer health insurance.