Fun fact:  we are composed of 90% bacterial cells and 10% human cells.  Surely, the company that begins to turn that knowledge into health products will be the next billion-dollar startup. Pendulum Therapeutics is doing just that.  Started in 2012, the company now boasts a full product line of probiotics that are not your typical probiotics.  In 2020, the company released a scientific study showing that their glucose control product lowered blood glucose spikes by 30%.“It’s the first microbiome product that has shown that kind of efficacy,” says Pendulum CEO Colleen Cutcliffe.  “We did a placebo-controlled double-blind, randomized trial that showed that compared to placebo, people who were on this formulation could see their A1C go down by 0.6 points, which can be the difference between having diabetes or not.”Colleen is a return champion here on the show, and it’s great to see the company raising real money and pioneering the microbiome space with credibility.  Will naturally occurring probiotics become the next breakthrough in therapeutics?  We’re talking about the "safety of a probiotic with the efficacy of a drug."

"We can now begin to look at disease before it happens,” says today’s guest, Todd Druley.  He’s the Chief Medical Officer at Mission Bio who has been offering the world’s first single cell and multi-omics instrument. 

This month, the FDA approved the first CRISPR-based gene therapy called Casgevy (pronounced with a soft g). It’s a one-and-done treatment for sickle cell disease and is being hailed as major step forward in medicine. Joining us to discuss this breakthrough is our return champion, Kevin Davies, author of Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing and Executive Editor of the CRISPR Journal and GEN Biotechnology.Kevin takes us into the science of the new gene therapy and what it means for patients. He also gives a captivating history of sickle cell disease itself. How will sickle cell patients afford the $2.2 million price list? How has CRISPR as a tool been evolving this year?  What other areas are heating up for gene therapy?  And we do a little catch-up on a certain scandal around genome editing. 

Many of our shows this year have explored a new wave of proteomics tools and research.  So today, we wanted to get a snapshot of the field of proteomics, and to do that, we turned to John Yates III, Ernest W. Hahn Professor at The Scripps Research Institute.  John was on the proteomics side of the famous Lee Hood lab in the 1980s.  The most exciting work to come out of Hood’s lab was the first automated DNA sequencer commercialized by Applied Biosystems and led by Mike Hunkapillar, also from the lab.

This month, a new philosophy of biology series premiers on PBS hosted by Robert Lawrence Kuhn.  The series will go for thirteen episodes and includes over 250 interview clips with some of the world’s leading biologists and philosophers, including Richard Dawkins, Terrence Deacon, Peter Godfrey Smith, and Samir Okasha. Show titles include: Why Philosophy of Biology?, Philosophy of Units/Levels of Natural Selection, and Philosophy of Sex and Gender.Robert joins us today to preview the series, his first in 25 years on biology.  At the heart of the interview is a discussion of reductionism and emergence,  a familiar subject for this show. 

John Shon is the Chief Technology Officer at Serimmune, a company specializing in precision immunology.  Serimmune maintains a library of over 10 million random peptides that can mimic almost any disease.  With this library, they are able to comprehensively map the relationship between antibodies and antigens.What does this mean?  Take COVID, for instance; rather than just offering a diagnostic, Serimmune can show disease history in the body.  They partnered with Moderna to look at the epitopes from their vaccines and boosters.  For those patients who took vaccines, the company saw a different and more focused response to the COVID-19 virus.This is a comprehensive measuring of human immunity.  The technology can be used with almost any disease.  And it picks up cross-disease interactions. So, where is the company today?  And how does John see their powerful technology being adopted in medicine?

Our guest today introduced us to a new kind of immunotherapy called Super-NK.  Imagine CAR-T, but in this case, the immune cells from the patient are not engineered, but rather “supercharged.”  What’s remarkable is that the company is having success with the therapy against neurological conditions such as Alzheimer’s and Parkinson's.Paul Song is the CEO of NKGen Biotech.  The company just presented results from a Phase I trial at the 16th Annual Clinical Trials on Alzheimer’s Disease Conference (CTAD), showing that enhanced killer cells could be an effective treatment against Alzheimer’s.  90% of patients demonstrated improvement or maintained stable cognitive function as per Alzheimer’s disease composite score (ADCOMS) following 11 weeks.Paul says that the idea of treating neurological disease with the super killer cells is quite novel and came somewhat randomly.  They had their sights set on treating cancer.“It’s by chance that we saw some activity with Alzheimer’s disease.  The co-founder’s father, sitting in a nursing home with advanced Alzheimer’s, wanted to know if we were to give him some enhanced NK cells whether that might make his immune system stronger to fend off an infection.  It was not to treat any neurological disorder.”Paul says they were confident that there were no safety issues and decided it was a reasonable thing to treat him.  After three or four treatments, the patient was talking to his son where he hadn’t been able to previously. “Nobody had ever heard of why an NK cell could cause improvement in neurological conditions.  There was nothing in the literature.”Now, with a Phase I trial showing great results, the company is excited to move forward in neuro and hopes to be treating patients by 2025.  What is the supercharging process?  Does Paul now understand more of the science behind these positive results?  And what is the biggest challenge moving forward?

Personalis, a company launched during the early days of whole genome testing and analysis, is claiming to have the most sensitive MRD testing available to date.  They are demonstrating this with the results of their recently released TRACERx study of patients with non-small cell lung cancer. CEO Chris Hall and CMO Rich Chen both join us to profile these exciting results and debut the entrance of Personalis into MRD testing. “This test is 10 to 100 times more sensitive than other tests,” says Rich Chen.  “And so how do we do this?  We’re creating a personalized test for each and every cancer patient.”First making their name in whole genome analysis, Personalis is not only looking at the ctDNA but also sequencing the tumor for each test.   The test is available now.  While the technology is validated for all cancers, Rich and John say they are going after the hardest-to-detect cancers first. What is their goal for the next two years, and how will the company push up the low rate of adoption in the field?   Join us for a comprehensive interview into the next generation of MRD testing.

Chapters:

0:00 Delivering on last year’s announcements

8:50 Illumina

14:25 Long reads

25:50 PacBio vs Oxford Nanopore

31:36 Element

38:27 MGI

45:47 The rise of proteomics

51:20 What next?

The end of the year approaches, and we look back today on the state of DNA sequencing with two of our return champions, Shawn Baker, genomics consultant, and…

Chapters:

0:00   State of the field: reviewing ICoNS conference

22:20 What evidence is enough?

Today, we’re joined by a panel of four guests who have all attended the recent International Conference on Newborn Sequencing held at the Royal Institution in London.  This discussion serves as the second part in a series we are co-producing with GenomeWeb that began with last month’s panel.  At the conference, researchers representing 12 newborn sequencing research programs in the US, the UK, Europe, Australia, and the Middle East discussed their progress to date and future plans.   It’s our good fortune to hear about the conference and get some thoughts on the field going forward.  Julia Karow is the Managing Editor at GenomeWeb, who tracks trends in next-gen sequencing for research and clinical applications.Robert Green is a physician-scientist who directs the Genomes2People Research Program in translational genomics and health outcomes.  He also co-chairs the International Consortium on Newborn Sequencing, the group which hosted the conference.Wendy Chung is Chair of Pediatrics in Medicine at Boston Children’s Hospital.  She directs one of the largest newborn sequencing studies,  called the Guardian Study.James Buchanan is a Senior Lecturer in Health Economics at Queen Mary University in London.  He does research into the health economics of precision medicine and genetic testing, including newborn screening.