#16 Trained Immunity (Mihai Netea)

Jorge L. Contreras is a Professor of Law at the University of Utah, specialising in Intellectual Property and Technology Law. He is the author of 150+ scholarly publications, alongside praised non-fiction books including “The Genome Defense: Inside the Epic Legal Battle to determine who owns your DNA” (2021). This book explores the AMP vs Myriad Case, which was sparked by patents litigations on the breast cancer gene BRCA for diagnostics, and historically determined that naturally occuring genes cannot be patented. Timestamps [01:00] Fundamental Principles of Patenting [08:30] Novelty and Utility in Patenting [10:40] BRCA and the AMP vs Myriad Case [17:00] Ethics of gene patenting  [23:30] The case for gene patents in biotech [28:15] Alternative intellectual property than patents  [33:00] Gene patents on pandemic pathogens [38:00] Patents in a globalised world [44:00] Future challenges in biotech patents  The Genome Defense Book Website : https://genomedefense.org A thought about the genome as a public good, like a shared universal truth contained in all life forms, and faithfully entrusted from one generation to the next  **Whoever has seen the universe, whoever has beheld the fiery designs of the universe, cannot think in terms of one man** (Borges, The God's Script (La escritura del Dios))

Barry Marshall is a Professor of Clinical Microbiology at the University of Western Australia. Alongside Robin Warren, he received the Nobel Prize in Physiology or Medicine in 2005 for first showing that Helicobacter pylori bacteria, rather than acid, were the cause of stomach ulcers. For this, Marshall did a self-experiment where he ingested H.pylori and gave himself acute gastritis, establishing a first link between the infectious agent and the development of gastric disorders.  We also embark on (a few) tangents:  [00:00] The acid theory of ulcers [09:20] Curiosity-driven research [11:10]  Self-experiment ingesting H.pylori [24:15] Non-invasive diagnostics [31:00] Peer-review  [40:45] Reproducibility [46:15] Unanswered questions around H.pylori [50:35] Bacteria as vectors  [57:45] Inflammation and cancer  [1:05:00] The Microbiome Revolution [1:13:20] Charles Darwin [1:18:45] Book recommendations [1:21:10] Karry Mullis Barry Marshall's blog: http://barryjmarshall.blogspot.com Barry Marshall's Nobel Lecture (2005): https://www.nobelprize.org/prizes/medicine/2005/marshall/lecture/ Kary Mullis' Book: Dancing Naked in the Mind Field (1998) Brother Surgeons: Brother Surgeons (1963) Garet Rogers

Thomas Pradeu is a CNRS Research Director in Philosophy of Science, leading a group at the ImmunoConcept called Conceptual Biology and Medicine. His group explores conceptual aspects spanning immunology, evolutionary biology, ageing and the microbiome.  We discuss: What Philosophy of Immunology is  How to assess the influence of an idea Misconceptions about the immune system The usefulness of the self/non-self framework Definitions of cancer in multicellular organisms How to integrate philosophy in science The ImmunoConcept lab page: https://immunoconcept.cnrs.fr

Prof Amaury Lambert is a mathematician, leading a research group called SMILE (Stochastic Models for Inference of Life Evolution) at the Collège de France in Paris. He is also a Professor at the Ecole Normale Superieure in Paris.  In this conversation, we discuss Mathematical definition of species Modelling the birth and death of species Using DNA sequences to infer common ancestors and species history Contingency in evolution Beauty in mathematics vs biology SMILE webpage: https://smile.cnrs.fr SMILE webpage at the Collège de France : https://www.college-de-france.fr/site/en-cirb/lambert.htm

Miles Carroll is leading a research group on High Consequence Emerging Viruses at the University of Oxford, and has previously worked at Oxford Biomedica and as head of research at Public Health England (PHE). This episode focuses on emerging viruses, which are viruses like coronaviruses and Ebola virus that have rising incidence or are increasing in distribution. We discuss: What makes an emerging virus successful Fieldwork during the West African Ebola outbreak (2013-2016) Using Nanopore sequencing and molecular epidemiology to track emerging viruses How to deal with the threat of future spillover events Miles Carroll Lab Page : https://www.well.ox.ac.uk/research/research-groups/carroll-group

Dr Minmin Yen (PhD) is the co-founder and CEO of PhagePro, an early stage bio-tech company spun out of the Camilli lab at Tufts University developing bacteriophage prophylactics against cholera, a diarrhoeal disease caused by Vibrio cholerae. Minimin Yen has been recognised by the MIT's Tech Review as 35 innovators under 35 for her work bridging biological engineering and public health.  In this conversation we discuss: The evidence that bacteriophages play a role in cholera epidemics The strategy of delivering lytic bacteriophages to prevent person-person transmission How we can compound the emergence of resistance in cholera bacteria Building trust in communities for adoption of experimental therapies The challenges of developing a biotech and manufacturing bacteriophage prophylactics Link to the PhagePro website: https://www.phageproinc.com Minmin Yen's MIT Tech Review article : https://www.innovatorsunder35.com/the-list/minmin-yen/

Prof. Mihai Netea is Head of the Division of Experimental Medicine at Radboud University (Netherlands) and group leader associated with the LIMES Institute in Bonn (Germany). He was the first to describe trained immunity, the ability of the innate immune system to display enhanced responsiveness to secondary stimuli. His group has studied the epigenetic modifications and metabolic reprogramming in trained immunity, especially in the context of BCG vaccination.  We discuss: Challenging dogma in immunology The epigenetic signatures and metabolic reprogramming occurring in trained immunity The evolutionary importance of trained immunity  Drug repurposing and nano-biologics to therapeutically target trained immunity  Rational use of trained immunity in vaccination strategies 

Sir Andrew McMichael is a Professor of Immunology at the University of Oxford and previously Director of the Weatherall Institute of Molecular Medicine. He is a fellow of the Royal Society and Academy of Medical Sciences and has been a leader in human immunology for decades, notably  focusing on responses to viral infections including influenza and HIV. We discuss: Prof McMichael's career in immunology spanning from his work in the 1980s on HLA restriction and recognition of viral peptides to the study of a HLA-E, an atypical MHC-Ib molecule that is involved in immunosurveillance  How HLA-E is involved in detection of the "missing self" by Natural Killer (NK) cells  The discovery of a class of CD8+ T cells recognising HLA-E complexes and their role in protection against SIV infection  The opportunities and unanswered questions in  HLA-E immunobiology Advice to scientists 

Sarah Fortune is a Professor of Immunology and Infectious Diseases at the Harvard T.H Chan School of Public Health and Director of the TB Research Program at the Ragon Institute of MGH, Harvard and MIT. We discuss her research into the interactions between Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB) and its human hosts. Specifically, we explore some approaches to explain the variability in infection and treatment outcomes, as Mtb infection remains asymptomatic in 90-95% of individuals but causes severe disease in others.  We discuss How bacterial and hosts determinants contribute to variability of outcomes A genome-wide strategy using CRISPR to identify target genes influencing the response to mycobacterial infection in macrophages The emerging roles of antibodies in the protection against TB disease The potential of technology-driven science in pushing the TB field forward Prof Sarah Fortune's lab page: https://sites.sph.harvard.edu/fortune-lab/ Link to the genome-wide screening of host:mycobacterial interactions discussed ( Open Access): https://pubmed.ncbi.nlm.nih.gov/32970993/ STOP TB Partnership : http://www.stoptb.org

This episode explores the contributions of theoretical physics to understanding biological evolution and self-assembly. Ard Louis is a Professor of Theoretical Physics at the University of Oxford and leads a group that uses computational tools to answer fundamental questions about the emergence and evolution of protein and RNA structures and gene regulatory networks. An attractive proposal developed in his recent work is that there is a bias towards simplicity in biological outputs, using the formalisation of complexity from Algorithmic Information Theory (AIT).  We discuss The historical role of theoretical physics in the life sciences The bias towards biological structures with low descriptional complexity  The concept of "Arrival of the Frequent" in evolution The usefulness of mathematics in describing biology Prof Ard Louis: https://www.physics.ox.ac.uk/our-people/louis Pre-print on the algorithmic nature of evolution :https://www.biorxiv.org/content/10.1101/2021.07.28.454038v2 Wigner's paper on mathematics in the natural sciences: https://www.maths.ed.ac.uk/~v1ranick/papers/wigner.pdf