The Translational Mixer

Andy Marshall

Two lapsed Nature editors, Andy Marshall and Juan-Carlos Lopez, have a conversation and a cocktail with experts in translational research and biomedicine

Episodes

  1. Episode 12: CHDI's Robert Pacifici on new treatments for Huntington's toasted with a Boulevardier

    APR 1

    Episode 12: CHDI's Robert Pacifici on new treatments for Huntington's toasted with a Boulevardier

    Send us a text Andy and JC get the lowdown from Robert Pacifici, CSO of CHDI Foundation, on the latest in Huntington's treatments from the recent 20th CHDI Therapeutics Conference in Palm Springs, California. Robert has spearheaded efforts at CHDI for the past 22 years, driving forward preclinical drug discovery programs and corralling efforts to develop bioassays, clinical biomarkers, patient-staging systems, clinical and regulatory consortia to galvanize industry efforts in this devastating and fatal neurodegenerative disease. Just four years after the field suffered several reverses for ASO therapies in late-stage clinical development, there is renewed optimism that a new set of disease-modifying therapies are within reach.    The Boulevardier  INGREDIENTS:  1 Oz bourbon (or rye)  1 Oz sweet vermouth  1 Oz Campari  Ice cubes  DIRECTIONS: Stir over ice for 45 seconds, strain into a rocks glass over a large ice cube, and garnish with an orange peel. Enjoy! --------------------- Check out presentations given at the 20th CHDI Therapeutics Conference here For a summary of the latest developments keep an eye out for a forthcoming news story at Nature Biotechnology Paper's mentioned in the conversation: Ai Yamamoto, José J Lucas & René Hen. Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's Disease. Cell 101, p57-66 (2000). The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    59 min
  2. Episode 10: Sebastian Giwa blazing a trail in organ storage/transplantation ...and a flaming Sambuca

    JAN 1

    Episode 10: Sebastian Giwa blazing a trail in organ storage/transplantation ...and a flaming Sambuca

    Send us a text Sebastian Giwa, co-founder of the Organ Preservation Alliance and the Biostasis Research Institute and serial entrepreneur, talks to JC and Andy about the promise of organ storage research in transplantation. Seb obtained a PhD in Economics at the Stockholm School of Economics and was named a Baker Scholar at Harvard and worked at Bridgewater Associates, Bain and Goldman Sachs. Since spending time at Singularity University/NASA's Global Solutions Program and working with the Obama White House, he has worked tirelessly to galvanize the new field of whole organ preservation seeking to massively expand the availability of donor organs for the hundreds of thousands of patients awaiting transplants.  Seb's ventures in preservation: Sylvatica Biotech (named for the wood frog that can survive freezing and developing supercooling technology to extend organ life), Ossium Health (bone marrow banking from deceased organ donors for patients with sickle cell anemia, leukemia, and lymphoma), and GaiaLife (human ovary vitrification for girls with cancer who have not yet reached puberty).  Seb's preferred digestivo: Flaming Sambuca ("Sambuca, ghiaccio e mosche"; roughly translated: “Sambuca, ice and flies.”) You will need: 1  2-1/2 oz shot glass 3 coffee beans 1.5 fluid Oz (44 mL) of sambuca 1 Butane lighter Directions:  Place the beans at the bottom of the glass. Pour in the Sambuca. Use the lighter (do not use matches containing sulfur or phosphorus; preferably long-reach lighter to avoid setting yourself alight!) to light the sambuca, then wait until the flame is low/blue and cover the shot glass with your hand to extinguish it. Groups mentioned: Bischof, J and colleagues. Physical vitrification and nanowarming at human organ scale to enable cryopreservation. BioRxiv. Physical vitrification and nanowarming at human organ scale to enable cryopreservation (November 11, 2024; non-peer-reviewed preprint). Rubsinky, B and colleagues. Bioengineering 10, (2023)   Kizer, KW et al (eds). Realizing the Promise of Equity in the Organ Transplantation System. (National Academies Press; Washington DC; 2022). "Five years ago, even top cryobiologists doubted that a human organ would ever be successfully frozen and thawed...My opinion has changed." Janet Elliott, Canada Research Chair in Thermodynamics at the University of Alberta. Scuddelari, M. Proc. Natl. Acad. Sci. USA 114, 13060-13062 (2017). Toner, M., and colleagues. The promise of organ and tissue preservation to transform medicine. Nat. Biotechnol. 35, 530–542 (2017). Uygun, K. and colleagues. Supercooling enables long-term transplantation survival following 4 days of liver preservation. Nat. Med. 20, 790–793 (2014) The Mixer music “Pour Me Another” courtesy of Smooth Moves!

    54 min
  3. Episode 8: Andrew Lo on fixing business models in biotech and a sparkling Mio sake!

    08/01/2024

    Episode 8: Andrew Lo on fixing business models in biotech and a sparkling Mio sake!

    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!

    56 min
  4. Episode 7: Anne Wyllie, COVID-19, the NBA and spit diagnostics washed down with a G&T!

    07/01/2024

    Episode 7: Anne Wyllie, COVID-19, the NBA and spit diagnostics washed down with a G&T!

    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!

    58 min
  5. Episode 6: Veronique Kiermer on open science and a White Negroni

    06/01/2024

    Episode 6: Veronique Kiermer on open science and a White Negroni

    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!

    51 min
  6. Episode 5: Nathan Price on scientific wellness and a Mojito

    05/01/2024

    Episode 5: Nathan Price on scientific wellness and a Mojito

    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!

    50 min
  7. Episode 3: Kiran Musunuru,  gene and base editors hit the clinic and a Bloody Mary mix

    02/29/2024

    Episode 3: Kiran Musunuru, gene and base editors hit the clinic and a Bloody Mary mix

    Send us a text 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!

    50 min

Ratings & Reviews

5
out of 5
5 Ratings

About

Two lapsed Nature editors, Andy Marshall and Juan-Carlos Lopez, have a conversation and a cocktail with experts in translational research and biomedicine