Mendelspod Podcast

Last month Dandelion Health, a healthcare data platform specializing in artificial intelligence and precision analytics, launched a public service to evaluate racial bias in health algorithms.  The company is partnered with three major healthcare providers in the U.S.

Most of the leaders of genomic medicine that we speak with say we are headed toward genome sequencing at birth.  Last year a first-of-its-kind study called the GUARDIAN began piloting just such medicine.  The ambitious multi-year study based in New York State is the brainchild of a titan in the field, Wendy Chung. 

Most of the leaders of genomic medicine that we speak with say we are headed toward genome sequencing at birth.  Last year a first-of-its-kind study called the GUARDIAN began piloting just such medicine.  The ambitious multi-year study based in New York State is the brainchild of a titan in the field, Wendy Chung. 

Ten years ago this week, the Supreme Court unanimously ruled that genes could not be patented.

  Today we feature Quantum-SI, one of the new wave of proteomics tools companies.  The company was founded by serial life science entrepreneur, Jonathan Rothberg, originally as a long read sequencing company.    Though the company pivoted to proteomics, they kept the sequencing part.

It's a thrilling time to be in proteomics.  Today we discuss a recent paper in PLOS One demonstrating how new technology has revealed a novel biomarker for non-small cell lung cancer previously undetected by other methods.  The paper could be a model for new proteomics research going forward.  Our guests are Margaret Donovan, Product Marketing Manager, and Asim Siddiqui, Senior VP of Research, both at proteomics company, Seer.

  SynBioBeta is the largest gathering of the synthetic biology community worldwide.  It's taking place May 23-25 in Oakland, California.  John Cumbers is the founder and CEO of the conference, and he joins us to talk about trends in the space and preview this year's confab. First, we discuss the impact Washington D.C. is having on the field.  What doe's Biden's love for bio mean for synbio? 

Philosophers talk about various kinds of knowledge.  There is knowing that something is.  We learn that the sun is 90 million miles from the Earth.  There is also knowing how to do something.  This includes skills we learn like riding a bike or cooking spaghetti.  Knowing how is different from knowing that.  

Long DNA has arrived.   Elegen, a new company based in San Carlos, California,  is out this year offering just long DNA.  According to their founder and CEO, Matt Hill and today's guest, the company's product is twenty times more accurate than anything else presently available. What does this mean for the world of biology and the world in general that we're seeing the emergence of a new subindustry devoted specifically to long DNA?

"We're not a sequencing company," says Molly He, CEO and co-founder of Element Biosciences in our first interview with the leader of the hot new sequencing company which seemed to come out of nowhere this past year. “We're a biology company.” Not a sequencing company? Element has just taken the lead in the race toward cheap clinical genomes, and their CEO is putting that news aside in today's interview. Instead, she's much more interested in touting the company's core technology “avidity.” The term comes from a core reagent the company has labeled an “avidite.”

Biology is complex, and the life science tool kit continues to expand to meet the challenge of that complexity taking us into the world of multi omics and beyond. Today we talk about 3D genomics and what this additional three-dimensional structural information is telling not just researchers, but clinicians, particularly in oncology.

Today we talk with Simon Fredriksson, CEO and co-founder of Pixelgen Technologies, a company just out of stealth offering spatial technology that maps cellular surface proteins at the single cell level. Called molecular pixelation, the breakthrough technology is designed to first target immune cells.

Editor's Note: Theral's mic malfunctioned in this interview. Fortunately the not as good backup mic did work and John has a good mic.  Our apologies. John Greally joins us today. He is the founding Director of the Albert Einstein College of Medicine's Center for Epigenomics. He's a pediatrician and a clinical geneticist with appointments in both at Einstein.

Last month the American Society of Human Genetics (ASHG) took a quite remarkable step, putting out a formal statement of apology for its past history of involvement with eugenics. Some say it's long overdue while some of us didn't know about this history.

23andMe occupies its own place in the world of genomics. Known for its vision to democratize human genomic information, the company has always gone big and bold, and sometimes controversial. Today we don't hear much controversy—is that because their approach has won out? In any case, they have certainly achieved a scale that surpasses any other genetic testing company.

Remember all those firsts for synthetic biology that we heard about coming from Craig Venter's company, Synthetic Genomics in San Diego? The first genome of a whole organism transplanted. First genome synthesized. First synthetic life created.

Oncology has emerged as the most successful disease area for precision medicine. Last year, as the genetic testing industry went through a royal shake-up brought on mostly by external market forces, it's been no surprise that precision oncology has been touted as a core strength. As the industry now works "to be more lean and profitable"--new language one hears these days, cancer testing will be a big part of that effort.

To begin the year, we head across the pond for an outlook on the thriving community of synthetic biology in the United Kingdom. Paul Freemont was a co-author of the UK's synthetic biology roadmap and co-directs SynbiCITE, the national center for the commercialization of synthetic biology. A few years ago the government put an initial investment of $300 million pounds into the field, and "everything was going swimmingly well," says Paul. "Then COVID happened."

Our goal with today's show was twofold: bring you a practical holiday gift idea and to take you into the world of a synthetic biology entrepreneur. Our guest: Zack Abbott, CEO of ZBiotics. Zack is a scientist turned businessman who is on a mission to change the conversation around GMOs. His first product is a genetically engineered probiotic that alleviates the morning-after hangover by breaking down acetaldehyde. Zack says he chose this product because it's something consumers can choose to take—unlike a medicine that's necessary like insulin.

When excitement around early cancer detection first surfaced, we heard about the “pan-cancer” test that would look for any and all cancers, and early. Now that we're some years into it, the approach is turning out to be more of a narrow one. Which cancer will we likely see targeted first with an FDA cleared test? Colorectal, according to today's guest.

Winter is here.  In America, we're just back from the Thanksgiving holiday when many of us travel and get together.  And so far there is no great COVID surge this year.  Or is there? Today's guest says there likely is, and we don't know it because of the most significant shift in our pandemic response: at-home testing.  

Winter is here.  In America, we're just back from the Thanksgiving holiday when many of us travel and get together.  And so far there is no great COVID surge this year.  Or is there? Today's guest says there likely is, and we don't know it because of the most significant shift in our pandemic response: at-home testing.  

Winter is here.  In America, we're just back from the Thanksgiving holiday when many of us travel and get together.  And so far there is no great COVID surge this year.  Or is there? Today's guest says there likely is, and we don't know it because of the most significant shift in our pandemic response: at-home testing.  

It's the age of multi omics. Or multi comics, if you don't catch spell check. A few weeks ago at the annual meeting of the American Society for Human Genetics, we were pleased to find not only genomics companies but some proteomics outfits finding a home. As we chatted with one of these, Olink Proteomics, we were blown away to hear that they were announcing the publication of 1,000 scientific papers. It wasn't so long ago that genomics companies were boasting this kind of milestone. Has proteomics finally achieved scale?

Pharmacogenomic testing, or PGx, is considered low-hanging fruit, a no-brainer for the application of genetic testing in the clinic. And some may think it is small fruit. Not so, says today's guest, Kristine Ashcraft. "Currently we lose a life every two minutes in the United States to non-optimized medications,” says Kristine in today's show. She has spent over twenty years working to see pharmacogenomic testing adopted into standard-of-care medicine. Kristine serves today as the Medical Affairs Director for PGx at the genetic testing company Invitae.

Last week with a crowd of 1,200 customers in a Los Angeles nightclub, sequencing company Pacific Bioscience launched two new sequencers, both long and short read, Revio and Onso. It was a night of great technology, music, and anticipation. Their customers have waited a long time for this moment. Revio offers long read whole genomes at scale for under $1,000.

Last week, during the first International Conference on Newborn Sequencing, a landmark study to sequence the genomes of 100,000 newborns was announced. Called the GUARDIAN study, the project is the brainchild of Wendy Chung, Professor of Pediatrics at Columbia University. The study will take place in New York State and is somewhat similar to an ongoing project in the U.K. being done by Genomics England.

Today spatial biology company, Vizgen, makes their debut on on the program. When Vizgen CEO Terry Lo was first involved in developing what we now call spatial biology at Perkin Elmer, he admits that he never thought it would have a genomics side to it.

One thinks of Invitae as a leading genetic testing company that has worked to improve clinical quality while bringing prices down. And they are, and they have. But after listening to today's show, you will see that their vision is bigger than that. Farid Vij is the President and General Manager of Data at Invitae. A year ago Invitae bought a company he co-founded called Ciitizen which was focused on providing patients with access to their complete medical records.

Have you ever heard of proximity ligation? We knew of it in research form back in the day, but not that it had been commercialized until this summer. It's not every day we come across a powerful new genomics tool on this program. Which begs the question, where have Ivan Liachko and his company, Phase Genomics, been hiding? The company received a grant this summer from the Bill Gates Foundation as well as the NIH to pursue phage therapeutics. That's using viruses to go after bacterial infections, particularly those which are developing antibiotic resistance.

Satellite Bio is named descriptively for the way its platform works. Out of stealth in the past few months with what you might call a middle ground approach to generative medicine between stem cell therapy and organ transplant, the company takes its name from the tissue therapy constructs they surgically implant in patients.

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.

In our age of specialization, today's guest, Dr. Will Hwang of Massachusetts General, went against the trend and received three bachelor degrees in different fields. Or is this the new trend? Will says that despite the diversity of pursuits, there was a thread that ran throughout his life as a student. He always liked to look at things at the fundamental unit.

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.

Arutha Kulasinghe was pumped for the AGBT (Advances in Genome Biology and Technology) Conference this year. He is the Principal Investigator for the Clinical-oMx Lab at the University of Queensland. Dr. Kulasinghe has pioneered spatial transcriptomics using digital spatial profiling approaches in the Asia-Pacific region, contributing to world-first studies for lung, head, and neck cancer and COVID-19. Not gathering last year due to the pandemic, the AGBT conference has became a kind of revival for genome biologists.

Dr. Eric Green has been the Director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) since 2009. Two years ago, he and his colleagues at the Institute came up with a strategic plan for the next ten years. Today we discuss the plan with the director and get his outlook on the future of human genomics. Dr. Green says human genomics can be roughly divided into four chapters.

There was a tweet thread at the end of the recent Advances in Genome Biology and Technology (AGBT) conference where researchers took a moment of silence for all the sequencing companies that have announced big plans at the conference and then died. It was clearly aimed at this year's sequencing tools entrant and buzz-generating Ultima Genomics. The company emerged from stealth the week before AGBT announcing the $100 genome with a purse of $600 million backed by funders including Khosla Ventures, Andreessen, and Founders Fund.

Has the pandemic unleashed the molecule of RNA to be the new future of drug development? Tim Mercer is the Director of the BASE Lab at the University of Queensland which has recently become one of Australia's leading national facilities for the manufacture and research of RNA technologies. Tim is the next guest in our series on enzymatic DNA synthesis which he says is "a quantum shift” in our ability to synthesize DNA. Tim then goes on to explore the future of mRNA vaccines and other RNA therapeutics.

Heidi Rehm's talents for genomics are legendary. Our field has devoured them like a hungry beast. Discovering an appreciation for the natural logic of genetics in her early school years, Heidi would later learn she was good at the standardization of genomic databases for clinical use. This would make her a pioneering superstar of genomic medicine.

The area of early cancer detection continues to become ever more exciting these days. Each month more companies add liquid biopsies to their product offering as new technologies advance and are able to recognize cancer with increased sensitivity and specificity, particularly from cell-free DNA in the blood.

In a genomics first, Pacific Biosciences has introduced a new method for detecting DNA methylation simultaneously with DNA sequencing. They are calling it 5-base sequencing. Today on the program, Jonas Korlach, PacBio's Chief Scientific Officer, and Tomi Pastinen, the Director of the Genomic Medicine Center at Children's Mercy Research Institute in Kansas City join us to describe the new breakthrough and connect it to clinical possibilities.

Pacific Biosciences has introduced a new method for detecting DNA methylation simultaneously with DNA sequencing. They are calling it 5-base sequencing. Today on the program, Jonas Korlach, PacBio's Chief Scientific Officer, and Tomi Pastinen, the Director of the Genomic Medicine Center at Children's Mercy Research Institute in Kansas City join us to describe the new breakthrough and connect it to clinical possibilities.

Alec Ford is passionate about his message. No wonder. There's an astounding fact in cancer medicine that is little known and could make a big difference. More cancer patients are dying from infections than they are from their cancers. And Alec's company has the technology to do something about it.

One of the underrated but true successes of precision medicine has been pharmacogenomics. Beginning in the '90s with the approval of the drug Herceptin for HER2 positive breast cancer, tailoring drugs to genotype has been one of the less controversial areas of our field and will only continue to build on the early promise of sequencing the human genome. Today we talk Michelle Whirl-Carrillo, Director of PharmGKB, a one-stop go-to for pharmacogenomics data that has been funded by the NIH since 2000.

In 1998, in a now-famous paper, molecular biologist Dennis Lo showed that cell-free fetal DNA is present in high concentrations in maternal plasma and serum. The finding has led to an explosive science based on cell free DNA and an industry that we all know as non-invasive prenatal testing. But more and more this science is making itself known in other disease areas, such as cancer, as well. Specifically, ctDNA is offering higher resolution in cancer treatment.

Today we talk with John Nelson, Senior Principal Scientist at GE Research and veteran in the field of DNA synthesis. On January 7th, 2020, two weeks before the first cases of the coronavirus were reported in the U.S, John and a team of scientists and engineers proposed a new project to DARPA called NOW, or Nucelic Acids on Demand Worldwide. The goal of the project, now fully underway, is to deliver DNA-based vaccines anywhere in the world in three days.

“I've seen a lot of revolutions. Now we're at the beginning of spatial biology, and I think it has the chance to transform life science similar to next gen sequencing, but even more. It's going to have more ramifications that spread through more disciplines than any of the revolutions I've seen in a while.”

Are we now entering the age of proteomics the way we did with genomics thirty years ago? We were told we should talk to today's guest by four people in one week. He's Omid Farokhzad, CEO and Founder of Seer Inc. When we did, we understood why. Seer offers its customers the chance to “see the proteome in a way that's never been possible before.” So what does that mean?

"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.