Episodes

  • Episode 9: Charles Fracchia on cyberattacks in biology...and downloading an Aperol Spritz
    Sep 1 2024

    Send us a text

    Andy and JC explore the murky world of cyberthreats to biopharma and biomanufacturing with Charles Fracchia, CEO of a Boston startup Black Mesa, currently in stealth mode and co-founder of BIO-ISAC, a BIO-Information Sharing and Analysis Center to educate about threat intelligence, vulnerability identification and mitigation strategies. Charles was previously CEO of BioBright, one of the first life science companies providing end-to-end encrypted data collection and analysis in the cloud.

    The Spritz Veneziano (aka Aperol Spritz)

    Ingredients:
    2 Oz Aperol
    3 Oz sparkling wine
    1 Oz club soda.

    Directions:
    Add the ingredients to a large wine glass with plenty of ice, mix gently, and garnish with an orange wedge.

    Amari that can replace the aperol:

    Campari
    Amaro nonino
    Amaro montenegro
    Averna

    Check out the resources on BIO-ISAC here: https://www.isac.bio/


    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    55 mins
  • Episode 8: Andrew Lo on fixing business models in biotech and a sparkling Mio sake!
    Aug 1 2024

    Send us a text

    https://bit.ly/3YxRltJ. Andrew Lo, Charles E. & Susan T. Harris Professor of Finance and director of the Laboratory for Financial Engineering at the MIT Sloan School of Management, gives JC and Andy the skinny on his progress in finding new commercialization models for rare diseases. He also reveals plans on implementing his debt securitization megafund model, first described over a decade ago. Finally, he gives us some tips on how to prepare a delicious refreshing sparkling sake:

    1) Mio sparkling sake
    1 bottle Mio sake
    1 freezer

    DIRECTIONS:
    From Andrew: "Store bottle of Mio at 58ºF (the recommended temperature of typical wine cellar). Move bottle to the freezer section of your refrigerator for about two hours before you're ready to consume it. The time is approximate, and depends on how cold your freezer is, so you may need to play around with this key parameter. After two hours, remove the bottle from the freezer; it should still be completely liquid inside (if it's partially frozen, you've kept it in too long and need to thaw it before opening).

    Assuming that the sake is completely liquid, twist open the bottle and QUICKLY POUR OUT A SERVING INTO YOUR GLASS. The reason you have to pour quickly is that the sake is sparkling, which means the carbonation creates pressure in the bottle. Once this pressure is released, the liquid starts to foam and the foam will freeze, clogging the bottle and making it impossible to pour out any liquid. By pouring it quickly, the foam forms in the class, yielding the desired frozen treat. The remaining liquid in the bottle is blocked by the frozen foam in the neck, but this will melt while you enjoy the first pour, and should be ready to be poured out in just a few minutes (though the foam won't be quite as thick in the second glass).

    This works best with Mio's individual 375ml bottles. It can be done with full 750ml bottles but it's hard to pour multiple glasses fast enough before the foam freezes in the neck (you have to line up your glasses and pour quickly in a straight line)."


    Sources mentioned in the podcast:
    Andrews new book:
    Andrew W Lo and Shomesh E Chaudhuri. Healthcare Finance (Princeton University Press, Princeton, 2023)

    Original paper describing megafund/securitization:
    Fernandez, JM et al. Commercializing biomedical research through securitization techniques. Nat Biotechnol 30, 964–975 (2012). https://doi.org/10.1038/nbt.2374

    Paper describing methodology for assessing risk (likelihood of approval) of biomedical assets:
    Siah, KW et al. Predicting drug approvals: The Novartis data science and artificial intelligence challenge. Patterns 2, 100312 (August 13, 2021).

    EU approval of Agilis Biotherapeutics/PTC’s Upstaza AAV2 gene therapy for delivering dopa decarboxylase to patients with aromatic L-amino acid decarboxylase (AADC) deficiency. As AAAC deficiency has an incidence of about 1 per 1,000,000 live newborns (332 potential US patients every year), a billion dollar return could theoretically be obtained in three years...in practice though the challenge for PTC is to find those patients!


    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    56 mins
  • Episode 7: Anne Wyllie, COVID-19, the NBA and spit diagnostics washed down with a G&T!
    Jul 1 2024

    Send us a text

    Anne Wyllie, principal investigator at the Yale School of Public Health and pioneer of the Saliva Direct initiative, talks to JC and Andy about the potential of open and collaborative models to transform infectious disease diagnostics and pandemic preparedness.

    1) The Gin & Tonic

    1 cup ice cubes
    2 Oz gin
    ~4 Oz Schweppes Tonic Water
    1 slice Lime/lemon

    DIRECTIONS:
    Pour 2 Oz gin into your favorite glass, ideally a large goblet full of ice, as shown. Top with ~4 Oz tonic water, mix gently, and garnish with lime or lemon.

    2) The Mediterranean Gin & Tonic

    1 cup ice cubes
    1.5 Oz Gin Mare (Spanish Gin)
    0.5 Oz Dry Vermouth
    0.5 Oz Sweet Vermouth
    ~4 Oz Fever Tree Tonic water
    1 sprig Thyme
    1 slice Lime/lemon

    Fill your favorite glass with ice. Pour 1.5 Oz Gin Mare (Spanish gin), 0.5 Oz dry vermouth, 0.5 Oz sweet vermouth. Top with ~4 Oz Fever Tree Mediterranean Tonic and mix gently. Garnish with thyme and lime/lemon.

    Sources mentioned in the podcast:

    Paper comparing saliva test to nasal/nasopharyngeal test: Overmeire, Y et al. Equivalence of Saliva RT-qPCR Testing to Nasal-throat/Nasopharyngeal Swab Testing in the General Practitioner’s Setting to Detect SARS-CoV-2. J. Pediatr, Perinatol. Child Health 6, 042-053 (2022). doi: 10.26502/jppch.74050089

    CDC COVID-19 testing guidelines (now including saliva)

    The COVID-19 testing debacle Nat Biotechnol 38 653 (2020)

    Saliva Direct and its test Emergency Use Authorization

    BBC News story on kids adding soda to get false positives in COVID-19 tests




    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    58 mins
  • Episode 6: Veronique Kiermer on open science and a White Negroni
    Jun 1 2024

    Send us a text

    Veronique Kiermer, Chief Scientific Officer and Executive Editor at the Public Library of Science, talks about the myriad ways in which open science is changing the face of research and some of the challenges it poses for AI and the translational arena.

    01:55 What is open science?
    03:55 What are barriers to openness?
    07:28 Early adopters
    10:30 Open challenges for AI
    11:35 Registered reports and publication bias
    14:20 PLOS’ priorities for open science
    18:40 The Open Science Village beyond data access and sharing
    24:25 Reproducibility and reuse in drug research
    27:30 Can biotech companies be as open as pharma?
    29:44 Pre-competitive consortia for rare disease
    32:14 Moving the needle
    38:00 Professional data curators?
    39:53 Opening science around the world
    41:05 COVID-19, infectious disease and open science
    45:34 Veronique’s favorite tipple

    The White Negroni
    1 Oz gin
    1 Oz Lillet Blanc
    1 Oz Suze

    DIRECTIONS:
    Add ingredients to a mixing glass and stir over ice for 45 seconds. Strain over fresh ice in a rocks glass and garnish with a lemon peel.

    Sources mentioned in the podcast
    Mehra, MR et al. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet (May 22, 2020) https://doi.org/10.1016/S0140-6736(20)31180-6).

    AlphaFold3—why did Nature publish it without its code? Nature 629, 728 (2024). Good question!

    Abramson J et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature (8 May 2024).

    Promoting reproducibility with registered reports. Nat Hum Behav 1, 0034 (2017). https://doi.org/10.1038/s41562-016-0034

    The Yale University Open Data Access (YODA) Project at the Center for Outcomes Research and Evaluation advocates for the responsible sharing of clinical research data

    All Trials (https://www.alltrials.net/news/)

    Gordon, D.E., Jang, G.M., Bouhaddou, M. et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583, 459–468 (2020).

    Nature’s podcast on Registered Reports: Nature's Take: Can Registered Reports help tackle publication bias?




    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    51 mins
  • Episode 5: Nathan Price on scientific wellness and a Mojito
    May 1 2024

    Send us a text

    Nathan Price, currently on leave from the Institute for Systems Biology in Seattle and Chief Scientific Officer at Thorne HealthTech, talks to JC and Andy about his data-driven approach to understanding health and predicting personal trajectories into disease as we age.

    03:24 What is scientific wellness?
    06:53 Correlates of scientific wellness

    15:45. Generating hypotheses
    18:40 Multimodal over unimodal data
    22:04. Biomarkers and individual disease trajectories
    28:00 How to intervene to maintain wellness?
    30:01 A new era for supplements?
    32:26 Single interventions versus combinations
    37:59 Racial background and lifestyle
    41:00 Digital twins, trial design and recruitment
    43:30 Mocktails and mojitos


    The Mojito
    10–12 mint leaves and mint sprig
    1 Oz simple syrup (50% sugar solution)
    2 Oz white rum
    0.75 Oz freshly squeezed lime juice.
    ~1–2 Oz club soda

    DIRECTIONS: Place the mint leaves in a shaker tin, add the syrup and gently muddle the leaves 10–12 times. Add the rum and freshly squeezed lime juice. Shake over ice for 15 seconds and double strain over fresh ice into a Collins glass. Top up with the club soda and mix gently. Slap a mint sprig to release the aromatic oils and add it as garnish.

    Sources mentioned in the podcast
    The supposed Native American 'diabetes gene'. Newman, AS. Peace Rev. 12, 517-524 (2010)

    Todd Rose. The End of Average (HarperCollins, 2016).

    Can a biologist fix a radio? Lazebnik, Y. Cancer Cell 2, 172-182 (2002) https://www.cell.com/cancer-cell/pdf/S1535-6108(02)00133-2.pdf

    Lancet Commission on risk factors for dementia: Livingston, G et al. Lancet 396, 413-446 (2020) https://www.thelancet.com/article/S0140-6736(20)30367-6/fulltext

    Precision Medicine Approaches for Developing Combination Therapies for the Treatment and Prevention of Alzheimer's Disease (AD) and AD-Related Dementia, National Institute of Aging, December 4-5, 2023.

    Khullar, D How to die in good health. New Yorker (April 15, 2024)


    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    50 mins
  • Episode 4: Dan Kaufman on off-the-shelf cell therapy and Manhattans
    Mar 31 2024

    Send us a text

    UCSD's Dan Kaufman, an innovator in the field of induced pluripotent cell (iPSC)-derived natural killer cell therapies, talks to Andy and JC about the latest in allogeneic and autologous immune and regenerative cell therapies at the 2024 Keystone symposium on Emerging Cell Therapies.

    02:55 Sourcing and expanding NK cells
    05:59 Off-the-shelf versus self
    09:26. Clinical trials and manufacturing
    13:40. Stealth, immune cloaking and protein manufacture
    16:51. Safety, cost, availability and standardization
    22:00. Stampede into autoimmune disease
    28:59. Neurological cell therapies and beyond
    33:30. Off the shelf and in vivo engineering
    38:13. Commercialization headaches
    39:51. Dan’s drink


    The Manhattan:
    2 Oz rye whiskey,
    1 Oz sweet vermouth,
    2 dashes aromatic bitters.

    DIRECTIONS: Stir on ice for 45 sec and strain over a coupe glass. Garnish with a maraschino cherry.


    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    44 mins
  • Episode 3: Kiran Musunuru, gene and base editors hit the clinic and a Bloody Mary mix
    Feb 29 2024

    Send us a Text Message.

    UPenn's Kiran Musunuru, a human geneticist and practicing cardiologist who has pioneered the translation of gene- and base-editing approaches, talks to JC and Andy about the latest clinical results and modalities discussed at the 2024 Keystone symposium on Precision Genome Engineering.

    4:07 Impacting patients
    6:44 In vivo editing in different liver diseases
    11:37 The FDA stance on programmable therapy
    19:41 Base-editors march into the clinic
    25:54 Multiplexing with base editors
    28:57 Reaching broader patient populations
    33:32 Investigator-initiated trials
    39:27 Prime and epigenetic editing
    44:34 Excitement around Bridge RNAs

    47:15 Kiran’s mocktail

    Bloody Mary 3 Ways
    4oz (120 ml) tomato juice
    1/2oz (15 ml) fresh lemon juice
    1/4oz (7 ml) Worcestershire sauce
    1/2 barspoon (3 ml) prepared horseradish, or to taste
    2 dashes Tabasco, or to taste
    Celery stick, for garnish
    Salt and freshly ground pepper
    Your choice of pickled vegetables, skewered on a cocktail pick, for garnish

    DIRECTIONS: Add the tomato juice, lemon juice, Worcestershire, horseradish, and Tabasco to a shaker tin with ice and gently shake for 5 seconds. Strain into a chilled double rocks glass over a large ice cube. Garnish with the celery stick, salt, pepper, and pickled vegetables and serve.

    For alcoholophiles, add 2oz (60 ml) vodka to the tomato juice, lemon, Worcestershire, horseradish and Tabasco. Enjoy!

    Refs:
    Gilmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. N Engl J Med 385, 493-502 (2021) DOI: 10.1056/NEJMoa2107454

    Chiesa et al . Base-edited CAR7 T cells for relapsed T-cell acute lymphoblastic leukemia. N Engl J Med 389, 899-910 (2023) DOI: 10.1056/NEJMoa2300709

    Longhurst et al. CRISPR-Cas9 In Vivo Gene Editing of KLKB1 for Hereditary Angioedema N Engl J Med 390, 432-441 (2024) DOI: 10.1056/NEJMoa2309149

    Durrant et al. Bridge RNAs direct modular and programmable recombination of target and donor DNA. https://www.biorxiv.org/content/10.1101/2024.01.24.577089v1

    Keystone Meeting on Precision Genome Engineering

    Somatic Cell Genome Editing Consortium


    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    50 mins
  • Episode 2: Eric Topol, multimodal AI models in medicine, and a glass of Merlot
    Feb 1 2024

    Send us a text

    Scripps' Eric Topol is a visionary in the application of artificial intelligence to medicine. He has a wide-ranging conversation with JC and Andy about :

    02:52 Multimodal AI is coming
    06:44 FDA-approved AI software
    10:02 How to validate AI models?
    12:50 Synthetic doctor’s notes and other early applications
    15:38 Thinking about the model and its training
    19:28 Dealing with hallucination and GPT5
    24:13 Low-to-middle income countries
    27:40 Uptake by the medical community
    29:15 Open or proprietary?
    35:46 What to do with the data?
    39:46 Eric’s elixir


    1) His September 2023 Science editorial,

    2) Derma Sensor.

    3) Wowser package AMIE (Articulate Medical Intelligence Explorer) a descendant of MedPalm 2

    4) A recent Science essay on diagnoses.

    Eric’s Elixir:

    Pinot Noir!

    Marimar Mas Cavalls Pinot Noir 2018 from Russian River Valley, CA, USA.

    Cristom Marjorie Vineyard Pinot Noir 2021 from Villamette Valley, OR, USA

    Racines Pinot Noir Santa Rita Hills 2017 from Santa Rita Hills, CA, USA



    The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    Show More Show Less
    42 mins