Mendelspod Podcast

We’ve all heard of and perhaps worked with data from The Cancer Atlas Project. Now, with the help of new spatial biology tools, researchers at the Mayo Clinic are developing what they call The Cancer Immunome Project. This is a comprehensive effort to fully characterize the immune system and how it interacts with and fights off cancer. Today we talk with J C Villasboas, a physician-scientist at Mayo who co-started the project. He’s also Director of Mayo’s Immune Monitoring Core Facility.

A discovery here. A paper there. An important paper gets passed over. A fortuitous encounter in a coffee shop among two ambitious scientists. A yogurt company just being a yogurt company. Science moves forward in fits and starts. By the time we read the headline in the paper, “breakthrough of the year,” it can have an inevitable quality about it. Then, in a few years, the historian comes and shows us just how random, messy, and, yes, how beautiful is the business of science.

At the beginning of the year, we were all holding our breath for the future of PacBio. And by all, I mean all. It seems everyone has been rooting for this sequencing technology company. And why? It’s simple. Pretty much everyone is in agreement that they have the highest quality reads on the market.

We speak directly with the Oracle today. It's Keith Robison, blogger at Omics Omics. Your All Knowingness, we ask, what has happened in the world of sequencing technology this year? “The companies may need a mulligan,” he quips and laughs.

Our October Review show is a Halloween special this year. Join us around the campfire amidst the sounds of howling wolves as Nathan, Laura, and Count Theracula recall some of their creepiest and spookiest times in the world of genomics. It's Mendelspod's Haunted House of the Genome.

There’s an urgency about Stephen Kingsmore. Which is not to say he’s in a rush. He’s the CEO of the Rady’s Children’s Genomics Institute. He and his team have two world records to their name for the incredible speed of diagnosing a rare disease using whole genome sequencing. The latest is 19.5 hours. Dr. Kingsmore feels they can even shave time off that. They’re shooting for a new record of somewhere around 12 hours.

Diversity’s in the news these days. It's not just political correctness. Let’s look deeper into our field at how limited diversity in genetics is affecting all of us. If you are a member of a minority population and you go into a cancer clinic seeking help, some of the genetic tests on offer may not work for you because of your ethnic background. Not only is this wrong on a social justice level. It turns out it's just bad science.

“In an era where we look at these surveys about trust and everything’s going off the cliff, everyone still trusts the NHS. It’s so deep in the British psyche."

We take a deep dive into a core genomics question that is somewhat philosophical today: “what is a disease, or disability?” This month we heard about a new experimental drug for dwarfism called vosoritide that raised questions for parents of dwarfism. If the drug could make their children taller, would they give it to them? Laura asks “can we put forth a medication for a condition saying those who take it are better off getting rid of it and not be saying those who are not getting it are unacceptable to have these different lives?"

From a career at NIH where he was Chief of the Genetic Disease Branch to academic Chief of Medical Genetics at UCSF to his current business title of Chief Medical Officer at InVitae, Bob Nussbaum has been a central figure in the field of genetic testing. A chief among chiefs. Today he gives our State of Genetic Testing: 2020 Edition. Our approach is to ask Bob to weigh into the recent debates that have come up this past year. And they can be summarized into one question. Even one word. "Expanded."

Synthetic biology was surging like perhaps no other bio-based industry when the pandemic struck, and it has had some unique weapons in its arsenal for aiding in the fight against COVID. There are the leading vaccine makers such as Moderna using synthetic biology, as well as antibody technology and CRISPR based testing. But many of the surging trends from the last year have only been made more urgent this year: small molecules, food tech, synthetic materials. Living with a pandemic is making humans more aware of our scientific dependence.

First it was all about biomarkers. Then panels of biomarkers. But biology is complicated. Why does one patient respond to an immuno therapy when another which shares the same biomarker does not? Welcome to the age of spatial biology. Garry Nolan joins us today. He's a professor in the Department of Pathology at Stanford who's career has been a journey of seeing intracellular happenings more and more in context. Check out this cool analogy from a new paper his lab put out in Cell.

After a long break, the world's first genomics pundits are back for the season. And they are calm and collected in the face of the strorm on Pennsylvania Ave. We're sixty days from an election. How serious should we be taking politicization of the COVID vaccine, this radical shift on LDTs at the FDA? We also discuss some regular approvals and on rejection that sent the industry reeling with disappointment. Then it's on to Laura's, Nathan's, and Theral's picks for science of the month. Welcome back!

We see this new ingredient appearing advertised and in products everywhere. On the billboards, in the new shops next to our favorite restaurant, on the counters at the barbershop and when we pick up our prescriptions at the pharmacy. C-B-D. It has to do with the ongoing revolution that’s happening around the country—around the world—regarding the deregulation of marijuana. But there’s another revolution that will change our consumption of cannabinoids. That of synthetic biology.

Mary Norton is a perinatologist and clinical geneticist at UCSF who says that in the age when we are diagnosing ever more rare diseases, adding to the carrier screening panel can be a good thing, but it’s complicated. But it can be a good thing. But it’s complicated.

Has this pandemic presented a unique moment for science in our history? Or is it just a strange and temporary moment of science fiction? Or both? Sci-fi author Kim Stanley Robinson (The Mars Trilogy, New York 2140 and Red Moon) recently penned an essay in the New Yorker about how the virus has “changed our imaginations” and created a new “structure of feeling.”

Happy summertime! We had positive news this month about an mRNA vaccine from Moderna. We also saw how during a pandemic, the process of science is especially abnormal. Nathan says let's be happy about the good news. Laura's ringing with alarm bells, sensing conflicts of interest right and left.

Back before the world turned upside down, you know, all those years ago--early this February--a paper popped up on bioRxiv called, “Nanopore adaptive sequencing for mixed samples, whole exome capture and targeted panels." It’s an interesting paper. In the paper, the authors, led by Matt Loose from the DeepSeq lab at the University of Nottingham, describe a method unique to nanopore sequencing where one can do "selective sequencing of single molecules in real time by individually reversing the voltage across specific nanopores.”

What is the key to getting a coronavirus vaccine? “Manufacturing,” says today’s guest, Jeff Stein of Cidara Therapeutics. Jeff joined us just last fall to talk about his company’s exciting new technology, an immunotherapy, that is a universal flu preventative and therapy. Yes, you read that right. A universal flu preventative.

Our commentators, Nathan Pearson of Root and Laura Hercher of Sarah Laurence College, join us to look back on month two of the first modern pandemic. We begin with a scandal that rocked the Twitter science community and talk about how science itself may be having a big moment. Will this be a silver lining for this strange year? Then it’s on to antibody testing. What would a good antibody test need to do? And will there be tough ethical questions when some “have their immunity papers” and go back to work while others do not?