The Revolution in Single Molecule Sequencing Continues: Vijay Ramani, UCSF

A new generation of biologists is pushing the limits of third-generation sequencing, furthering the technology's development and defining new applications to answer biology’s most pressing questions.

This is the express goal for the lab of Vijay Ramani, assistant professor at UCSF in the department of Biophysics and Biochemistry. Vijay also has an appointment in the Institute of Data Science and Biotechnology at the Gladstone Institute, and in 2019 he was named to the Forbes 30 under 30 rising stars in healthcare list.

Today Vijay shares his recent work to characterize the structure of the chromatin fiber which he says could not have been done on short read technology. Vijay uses epigenetic tagging to measure chromatin, a technology unique to 3rd generation sequencers.

One of the drawbacks to small molecule sequencers has been the large sample size needed. In a recent breakthrough, Vijay and his group published a preprint with a protocol for 1/100th the sample size. This opens up PacBio sequencers to a host of new applications, such as clinical and metagenomic work.

Vijay’s lab has been up and running for four years now. What does he see on the horizon for sequencing? What technology improvements does he desire? And what does he make of the short read scale, scale, scale argument?

Lee Cronin on Origin of Life, Genomics, Aliens and More

While we’re able to sit outside on a warm summer’s night under the ocean of stars, let us contemplate some of the bigger questions.

We’re very excited to start out our twelfth season of the podcast with the chemist, Lee Cronin, from the University of Glasgow. Lee published an original and fundamental theory about the universe in the weeks after we taped which has profound implications for the question about the origin of life and could have some interesting applications in genomics.

Here’s Lee on what he calls assembly theory:

“Darwin’s theory of natural selection is a very natural phenomenon in biology. But it hasn’t been given any precision in mathematics or physics even though there is plenty of computational evolution. Genomics has allowed us to do this. But before genomics, how does evolution work? Assembly theory gives you the mechanism by which you can get selection before biology, selection before genes. And by extension, genes are just a product of assembly theory. And because we have a mathematical basis for assembly theory it should propagate well into genomics.”

How often does a scientist come along with a theory on par with natural selection? We often ask biologists on this program if they are reductionists—if they believe biology can be reduced to chemistry. When we asked Lee, he answered that he is an “assembly theorist.” So is that a category now? And can one be an “ist” of their own theory? Why not—what’s the fun of coming up with a theory if you can’t? If discussing abiogenesis isn’t cool enough, Lee talks about applications this theory might have in the study of genomics and biology today.

We then roam into questions of death—what are Lee’s thoughts on radical life extension?—and cancer cells. And from there to aliens. Lee’s unusual thinking on that topic is that life elsewhere will be much stranger than most of us have been thinking. He doubts that any alien life would stem from RNA.

One of Lee’s current projects is chemical computers which he designed because he was fed up losing grad students who were trained to make chemicals. The computers create chemicals now for a company called Chemify.

Cutting through the Hype in Healthcare Innovation with David Shaywitz and Lisa Suennen

In today’s special studio interview, the health tech duo, David Shaywitz and Lisa Suennen, walk us through the changing paradigms around healthcare. They offer their thoughts on some of the new digital health and peer-to-peer social platforms which are becoming integrated in daily clinical care.

Lisa grew up in Silicon Valley and is an investor in the health tech space. David is a newcomer to the Valley and is currently the Chief Medical Officer at DNAnexus, a company that provides cloud based genomics data storage and analytics. They are both avid bloggers and recently compiled much of their written work together into a book, "TechTonics: Can Passionate Entrepreneurs Heal Healthcare with Technology?" They also co-host a new podcast by the same name.

A Call to Consumers to Lead the Shift in Healthcare: Sharon Terry, Genetic Alliance

One of those attending the recent White House gathering where Obama announced the Precision Medicine Initiative was a woman who has worked tirelessly as a patient advocate for over twenty years. She’s an award winning scientist and the CEO of the Genetic Alliance: Sharon Terry joins us to kick off a new series, Personalized Medicine and the Consumerization of Healthcare.

Sharon was advocating for the sharing of patient data long before it became fashionable. Recently chairing the Institute of Medicine’s workshop and consensus study on data sharing and clinical trials, Sharon says that there has been a shift on the topic and that we are finally saying how do we share, not do we share.

“My desire is that we consumers—patients, participants, public—whatever word you want to use—that we understand how much power we have to shift the paradigm. Other industries have shifted—music, publishing, banking—because consumers demanded certain things,” she says in today’s interview. "I think we may have to be in the same position in health and medicine. It may have to come from us more than anywhere else. And then economies will be built around that sharing that right now don’t exist."

A Dangerous Book? Science Historian Nathaniel Comfort Discusses “A Troublesome Inheritance”


Comfort, Nathaniel, PhD, Author, Professor, History of Science, Technology and Medicine, Johns Hopkins University

Bio and Contact Info

Listen (4:20) Debate about race and genetics is really about social justice

Listen (2:32) The radical middle

Listen (4:45) How to define race when genetic variation is continuum

Listen (6:03) As a society are we trusting science more as the ultimate source of knowledge?

Listen (6:04) Does Wade's book help free scientists and clinicians?

Listen (2:04) On blogging

Is race biological, or is it a cultural construct?

This question lies at the heart of a debate sparked by this year’s publication of “A Troublesome Inheritance: Genes, Race, and Human History.” Writing that race is biological, former New York Times science journalist, Nicholas Wade, ignited a furor in the life science community, with many scientists denouncing the book and the misrepresentation of their research. Science writer, David Dobbs, called it a “dangerous book.”

Joining us today to work through some of the tough questions in this debate is Nathaniel Comfort, a science historian at Johns Hopkins University. Comfort describes his position in the debate as the “radical middle”, accepting some of Wade’s arguments but insisting that science is always in a context, that it’s always political.

“The debate over race and genetics is really about social justice,” Comfort says in today’s show.

Comfort argues that Wade is not honest about the book’s agenda and uses science as a proxy argument for his own preconceptions. Comfort warns that genetic explanations, such as the one Wade makes for race, usually tend to reinforce the status quo.

So what about using race as phenotype for treating various diseases? For example, some racial groups are more likely to get certain diseases than other groups. Working at a major medical research facility, Comfort has the opportunity to talk to clinicians on a regular basis about whether, in today’s world of personalized medicine, race is still relevant as a phenotypic marker.

For more, visit Comfort’s blog on the topic.

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Are We Driving Innovation without the Quality? Pete Kissinger, Purdue


Pete Kissinger, Chemist, Purdue University
Bio and Contact Info

Listen (4:43) Many problems in life science traced back to poor measurements

Listen (2:50) Innovation without quality

Listen (4:37) Metabolome closer to reality than genome

Listen (7:46) Too focused on questions of reimbursement and regulation

Listen (3:34) Smartphone bio sample collection not there yet

Listen (10:35) Does the new Emerald Cloud Lab have a future?

Pete Kissinger is one of those who can discuss just about any area in the life sciences, often with humor. Pete's a professor of analytical chemistry at Purdue and founder of a drug development company, Bioanalytical Systems.

When I first chatted with Pete, our discussion went to every corner of the industry and back again. If Pete were a football player, he'd be comfortable in any position from quarterback to front linesman to safety.
For today's show, Pete and I tried to stick to a common theme--the importance of quality measurements.

Pete ties many of the problems we have in the life sciences--issues of reproducibility, failed clinical trials, an over emphasis on genomics--to low quality measurements. When asked why that is, Pete turns to funding, arguing that we are prioritizing the new over the reproducible.

"Often there isn't the funding to validate sufficient numbers of samples . . . We fund innovative academic science. We don't fund the routine blocking and tackling required to get quality data from a sufficient number of subjects," he says in today's interview.

At the end, I ask Pete what he thinks about the new Emerald Cloud Lab, a remote lab offering basic biology experiments accessible to anyone through the cloud. Will this impact the integrity of the scientific method?

But often we get off track. Pete is too fun a guest not to loosen the reins a bit.

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Join Us Next Week for a Discussion about the Challenges of Data Visualization and Reporting in Genomic Medicine

Next Thursday, June 5th, Mendelspod teams up again with Chempetitive Group to bring you an evening of networking and a special panel discussion.

"Delivering Genomic Medicine: Challenges in Data Visualization and Reporting"

When:  Thursday, June 5th

   Networking:  5 30 pm

   Panel Discussion:  6 15 pm

Where:  Omicia Inc, 1625 Clay St, Oakland, CA  94612

Why Scientists Should Study Philosophy

Since the first human genome was sequenced, there has been disappointment in and with the life science community over the fact that we haven’t figured out more of the big biology problems.  Cancer, for instance.  Oh, there’s been rapid technological progress.  Illumina announced this year that the human genome that cost $3 billion to sequence originally can now be done for the cost of a root canal, or $1,000.  

So why the disappointment?  Why were scientific expectations so high?  


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