Mendelspod Podcast
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"There's an entire field of fragmentomics with a whole lot of people working on it. The DNA which is shed into the bloodstream has a certain length. The length of ctDNA is shorter than cfDNA, and depending on where the cancer cell is located, the fragment size and pattern is different. So you can actually deduce information about the tissue of origin from the fragment length and pattern. And that's just the beginning."
The DNA synthesis space is seeing some real creativity and disruption this past year. One newcomer, in particular, is shaking things up. Sylvain Gariel is the co-founder and chief operating officer of DNA Script, who has recently launched the world’s first benchtop enzymatic DNA synthesizer. In today's show, Sylvain, co-inventor of the new system, tells how he met his co-inventors at a French gas company and came to invent a whole new way of writing DNA.
Even though Brian McKelligon calls himself a rookie CEO, he comes to the top position at Akoya Biosciences with a veteran’s resume. His path to one of spatial biology’s hottest companies in 2022 worked him up the ranks of some of the top names in life science tools: Affymetrix, Ingenuity, Ion Torrent, and 10X Genomics. Last year Brian led Akoya through an IPO and this year the company has launched a new integrated product line called the Phenocycler-Fusion which they are calling the fastest single-cell spatial biology system on the market.
Harlan Robins is the Chief Scientific Officer at Adaptive Biotechnologies in Seattle. In 2014, Harlan and his brother Chad co-founded Adaptive as a spinout from the Fred Hutchinson Cancer Center where Harlan had served as the head of computational biology. Adaptive has been developing what they call "immune medicine" mainly in the area of cancer. When the corona virus pandemic hit, they came out with the world’s first T cell-based COVID diagnostic. The test has garnered them a lot of data on T cell response to COVID.
“DNA is changing everything for the better,” says today’s guest, Emily Leproust, CEO of Twist Bioscience. Twist has emerged at the heart of what a New York Times Magazine write-up recently headlined The Gene Synthesis Revolution https://www.nytimes.com/2021/11/24/magazine/gene-synthesis.html.
Working at the Broad Institute early in his career, Michael Schnall Levin was discovering he was a biologist at heart. He’d begun his studies in physics then done his PhD in mathematics. But he'd wanted “to do math that had an application in the real world.” It was at the Broad that Michael came in contact with the new tools that were revolutionizing biology.
According to scientists, 30,000 species per year are going extinct. That’s 6 an hour, 150 per day. Up to one half of all species could be extinct by 2050.
Chris Mason is back on the program for our end-of-year special. He’s Professor of Genomics, Physiology, and Biophysics at Weill Cornell School of Medicine and the author of such an outstanding book that we had to have him on the program a second time this year.
In a joint interview, Sean George, CEO of diagnostics firm, Invitae, and Christian Henry, CEO of sequencing tools company, Pacific Biosciences, say that “it was clear in the first five minutes of a phone call that they shared a vision for doing something big together.” What comes through the interview is that this partnership is built on a big vision: speeding up the adoption of whole genome sequencing into clinical medicine as the preferred method for genetic testing.
There are some technologies that become so ubiquitous in biomedical research that their name turns synonymous with their use. This has been the case for the Luminex xMAP platform and multiple biomarker analysis. The product has been applied in just about every area of life sciences including infectious disease, STD, organ transplant rejection, vaccine development, cancer research, immunodeficiency, animal testing, agriculture, and others. (xMAP is a research use only product and not for use in diagnostic procedures.)
DNA is a multibillion-dollar industry in 2021 and satisfies many life science applications, including drugs, reagents, siRNA, PCR, diagnostics, synthetic biology, and many others. Enzymatic DNA synthesis, or EDS, is a new approach to manufacturing DNA that is much more efficient and user-friendly and could disrupt the current market.
If one was going to be a cancer researcher, surely one would want to be Christina Curtis. She’s an associate professor of oncology and genetics at Stanford, and she studies tumor evolution. She’s the Darwin of cancer research. Because scientists can’t see human tumors evolve in real life, in Christina's lab she creates what she calls "virtual tumors that recapitulate the size and spatial properties of an actual tumor. And evaluating patient data,” she says, "we have found that metastatic seeding could happen very early. That these tumors were born to be bad.”
"Scientists have been putting RNA into cells through a lipid delivery system for 44 years,” says Elie Dolgin. “And that’s ultimately the vaccine that has gone into millions of arms.” Elie is the author of a recent piece in Nature magazine, The Tangled History of mRNA Vaccines https://www.nature.com/articles/d41586-021-02483-w. He joins us to talk about his quest to uncover the winding journey that led to the cure that is moving the world forward.
“Why do plants make a host of chemicals they don’t use? One answer that has always intrigued me is that, unlike us, they can’t walk up and walk away from an environment they don’t like. Evolution has honed this space for over 400 million years.”
David Rimm, Professor of Pathology at Yale, was doing spatial biology since before it was called that. He’s known for counting. And he’s been going beyond—beneath?--the model of the cell in biology for years.
Carlo Bifulco joins us today. He’s an Italian who helped persuade one of America’s largest not-for-profit health systems that providing more genomic information to cancer patients early on was the right thing. With 52 hospitals, over 1,000 physician clinics, more than 120,000 caregivers serving communities across seven states—Alaska, California, Montana, New Mexico, Oregon, Texas, and Washington—Providence and Carlo have quite a task ahead. We ask Carlo what is the state of comprehensive genomic profiling at Providence today?
If a company knows genome engineering, that would be Emeryville based Amyris, the Bay Area's crown jewel for synthetic biology. Founded back in 2003, the company first worked on creating biofuels from yeast. Today they have retooled their platform to produce a diversified line of consumer products that have not only rewarded their bottom line but point the world to a model of sustainable consumer goods.
Laura Hercher, host of our sister podcast, The Beagle Has Landed https://beaglelanded.com, joins us today to compare notes. Her gig is much more focused on the clinical side of genomics. Genetic counselors are her core audience. Today we do a highlights show looking back over the Beagle's past year.
Chris Mason, Professor of Physiology and Biophysics and prolific genomics researcher at Weill Cornell Medicine, joins us to talk about what he’s doing with the new generation of spatial biology tools. The first papers we dive into are his work on COVID. Chris says the spatial tools have shown us the ravages of the coronavirus on the body like nothing we’ve seen before, i.e. the tissue damage from the cytokine storms and “the long term perturbations such as seeing cells far apart that were usually hanging out together.”
David Steffin is a cancer researcher and physician at Texas Children's whose particular focus is on pediatric cancers. He begins today’s program with some interesting numbers.
"If you go to a scientific meeting, even with the greatest critics, and you ask, how many people in this audience believe that your entire genome will be part of your everyday medical care in fifty years, every person will raise their hand. So the only questions we’re debating are: how do we get there, how soon can we get there, and what evidence base must we have in place before we get there? What’s really exciting to me is getting there sooner rather than later. If we get there 20 years sooner, we are saving thousands of people's lives.”
We’re all aware of the way that next gen sequencing has changed many tests in the clinical laboratory. But some testing has held stubbornly resistant to change. This has been the case in cytogenetics, or the analysis of chromosomes. That is now changing thanks to a technology that is making inroads where next gen sequencing could not.
"We have all of these evidence based tools and evidence based methods, but the problem is it can take upwards of 20 plus years to be truly implemented into care where healthcare providers are using them and patients are receiving them. And this includes medications and diagnostic tools and other types of treatment or screening.”
One of the hottest new trends in biomedical research today is what is known as spatial biology--the ability to capture tissues in a 3D context. It was named Method of the Year https://www.nature.com/articles/s41592-020-01042-x by Nature Magazine in 2020. And one of the first automated instruments launched in this market was the GeoMx Digital Spatial Profiler by NanoString. CEO Brad Gray is here to tell us the story of the birth of the DSP and the revolution of 3D biology. What will these new tools enable for the basic and translational researcher?
When Lee Schwartzberg did his training as an oncologist some thirty years ago at Memorial Sloan Kettering in New York, he had a dream. And after training, he set off to make that dream a reality: to bring the resources, expertise, and research that one enjoys at a major research hospital cancer center to the community level.
“The new drug is the engaged individual,” says today’s guest, Daniel Kraft. Daniel is the founder of Exponential Medicine where he has championed digital health and the explosion of wearable technologies. He's also hosting the new Healthy Conversations https://cvshealth.com/news-and-insights/programs/healthy-conversations podcast--go check it out! There you will find interviews with the innovator’s of today’s medical culture, including shows with former FDA Director, Scott Gottlieb, and genomic medicine guru, Eric Topol.
First comes love, then comes marriage; then comes the genomic couple's report. Isn't that how the line goes? Perhaps that's a how it will begin to go. Today's guest is the founder of Orchid Health, which as of this week is offering the world’s first risk prediction couple’s report https://www.orchidhealth.com. Based on whole genome sequencing from a saliva sample that expectant parents take from home, the report will tell them their genetic risk for the major diseases, including brain, heart, cancer, diabetes, and inflammatory bowel.
Will there be a fourth surge of COVID here in the U.S.? Already that we’re asking the question and it’s not an inevitability is a good sign. It’s become a race between vaccination clinics and viral variants. The U.S. was a bit slow to this race, but we are catching up. Viral surveillance has become a key part of any nation’s pandemic strategy. This past month, PacBio and Labcorp announced a partnership that brings the tool of long read sequencing to this effort.
Kevin Hrusovosky’s career has been dedicated to transforming medicine from reactive “sick care” to preventative personalized care. A serial entrepreneur, he currently serves as the CEO of Quanterix, a company which has just nabbed $700 million and is raising the bar on proteomics testing. “Genomics can tell you what your predisposition is,” he says in today’s interview, “proteomics can tell you the earliest moment you are in a disease cascade.”
Raj Krishnan has a good story, and probably a good product. More data will tell. He's the CEO of Biological Dynamics, a new liquid biopsy company that is able to detect biomarkers in not only blood but other biological fluids. And the company's products are good for not only cancer but Alzheimer's and other disease areas as well. Raj comes to precision medicine from electrical engineering. You don't hear that very often. One day in his lab while working on his PhD he had a classic eureka! moment. That unexpected discovery for which every scientist longs.
