Two Scientists Walk Into a Bar

We published our first episode on the threat of antibiotic resistance in 2016, and nearly a decade later, it remains one of the world's most pressing health crises. Today, with advances in artificial intelligence (AI), the race to develop new antibiotics is evolving. In this episode, co-host Danielle Mandikian sits down with guests Tommaso Biancalani, Distinguished Scientist and Director of Biological Research and AI Development, and Steven Rutherford, Senior Principal Scientist and Director of Infectious Diseases in Research Biology, to share the latest in the fight against antibiotic resistance. Together, they discuss the challenges of antibiotic discovery and development, and how AI could streamline the process of identifying novel antibiotics within the vast, uncharted chemical universe. Read the full text transcript at www.gene.com/stories/ai-and-the-quest-for-new-antibiotics

As we kick off season six, we're diving deeper into one of our most popular topics from last season – our evolving understanding of obesity. In this episode, co-host Maria Wilson unpacks the latest in obesity biology and management with Manu Chakravarthy, Senior Vice President and Global Head of Cardiovascular, Renal and Metabolism Product Development, who discusses the stigma associated with obesity and how thousands of years of human evolution contribute to this chronic condition. While lifestyle, diet and exercise modifications are still essential in addressing the biological factors that drive obesity, they explore how emerging treatments have the potential to rewire the brain's hunger and satiety signals – offering a more personalized, sustainable approach. Read the full text transcript at www.gene.com/stories/digging-deeper-into-obesity

Join Danielle Mandikian and Maria Wilson as they kick off season six of Two Scientists Walk Into A Bar. Hear what they've been up to in the past few months and enjoy a sneak preview of the exciting topics ahead. This season, we're focusing on unmet needs and will dive deeper into lung diseases, regenerative medicine, and cell therapies. We'll also check in on the latest advances in obesity, antibiotic resistance, and AI in drug discovery. We've got an impressive lineup of brilliant guests that you won't want to miss! Subscribe today to get notified about our latest episodes. Read the full text transcript at www.gene.com/stories/season-six-teaser

Machine learning and generative AI are transforming the ways we live and work, but how do these tools fit into the landscape of drug discovery? In our season 5 finale, co-host Danielle Mandikian is joined by Rich Bonneau, Vice President of Machine Learning, Drug Discovery, to break down the fast-paced, expansive – and sometimes perplexing – world of AI and biology. Together, they discuss the importance of integrating machine learning with traditional lab work, the need for minimizing bias in datasets, and the exciting potential for these technologies to unlock better and more complex medicines. Read the full text transcript at www.gene.com/stories/ai-and-the-future-of-medicine

Small molecules, antibodies, gene therapies – there are so many types of medicines scientists can consider when developing a new treatment for a disease. In this episode, Karin Briner, Senior Vice President and Head of Drug Discovery, joins co-host Maria Wilson to break down different therapeutic modalities, or types of treatments. Together, they cover a wide range of modalities in our drug development toolbox – including RNA-based therapies, large molecules, cell therapies, and newer small molecule approaches like protein degraders – highlighting the challenges and opportunities presented by each while also providing a look ahead to innovations that could lead to more effective treatments for a range of diseases. Read the full text transcript at www.gene.com/stories/a-deep-dive-into-drug-modalities

Did you know that scientists can grow three-dimensional, miniature versions of human organs in a dish? These tiny in vitro models, known as organoids, are helping scientists to better understand human disease and to test new treatments. In this episode, co-host Danielle Mandikian sits down with Kim Homan, Senior Director and Distinguished Scientist, Complex in vitro Systems Lab, to discuss the fascinating world of organoids and organ-on-chip technologies. They delve into how these systems are transforming drug development, where AI and ML come into play, and how organoid models could lead to more accurate predictions, better clinical studies, and improved patient outcomes. Read the full text transcript at www.gene.com/stories/organoids-from-dish-to-discovery

To defeat cancer, we need to understand it better. How does it grow? How do we detect it early? And most importantly, how do we treat it? In this episode, co-host Maria Wilson chats with oncology expert Louis Vermeulen, VP and Senior Fellow, Discovery Oncology, about what's new and exciting in cancer research. Together, they explore the importance of early detection, explain concepts like the tumor microenvironment, discuss cancer treatment approaches, and dive into how tools like artificial intelligence are accelerating research in the oncology space. Read the full text transcript at www.gene.com/stories/cancer-conversations-early-detection-and-potent-solutions

What drives metabolic conditions like obesity? In this special episode, co-host and cardiovascular disease expert Maria Wilson, gRED Executive Director and Cardiovascular and Metabolism Research Head, takes the hot seat with fellow host Danielle Mandikian, gRED Senior Principal Scientist, to discuss the complex world of obesity. Tune in to hear about the biological and environmental factors contributing to this chronic disease, its profound effects on health, societal implications, as well as the latest and upcoming treatment approaches for obesity and related metabolic conditions. Read the full text transcript at www.gene.com/stories/the-streets-and-deets-of-obesity

Antibodies are proteins produced by our immune system that neutralize or help destroy abnormal cells and foreign agents, like bacteria and viruses. However, their utility extends beyond our bodies' defense system. Antibodies can also be engineered in the lab to be used as therapies. Today, over 170 antibodies have been approved as medicines to treat a wide range of diseases including cancers, autoimmune diseases, infectious diseases and more. In this episode, co-host Maria Wilson chats with guests Yan Wu, VP and Senior Fellow, Antibody Engineering, and Paul Carter, Genentech Fellow, Antibody Engineering, to discuss all things antibodies! Learn about the history of therapeutic antibodies, how advances in antibody engineering are creating new classes of medicines, and the promising role of artificial intelligence in designing antibodies from scratch and optimizing their therapeutic activity. Read the full text transcript at www.gene.com/stories/engineering-therapeutic-antibodies

Many health conditions require medicines that can be delivered to specific parts of the body. For instance, someone with asthma requires medication that targets the lungs, while someone with a neurodegenerative disease needs therapeutics that can penetrate the blood-brain barrier. But how do scientists create medicines that not only reach their intended targets but also produce the desired pharmacological effect while minimizing side effects and ensuring convenience for the patient? In this episode, co-host Danielle Mandikian chats with Karthik Nagapudi, Executive Director of Pharmaceutics, to explore the pivotal role of drug delivery strategies, highlighting how incorporating drug delivery considerations from the initial stages of drug development is crucial for creating next-generation medications. Read the full text transcript at www.gene.com/stories/no-delivery-no-drug

Imagine the eyes as cameras, where the cornea acts as the lens and the retina as the film. As with a camera, if something goes wrong in the eye, it needs to be fixed to address the specific problem and restore function. While some visual impairments can be corrected with glasses or surgery, some conditions require medicines – like those that slow or stop blood vessel growth in the eye. In this episode, co-host Danielle Mandikian joins guests Chris Brittain, Vice President and Global Head of Ophthalmology Product Development, and Dolly Chang, Group Medical Director, gRED Early Clinical Development, to explore the evolution of eye treatments, advancements in current solutions for vision loss, and their insights into the future of treating ocular diseases. Read the full text transcript at www.gene.com/stories/seeing-clearly-the-past-present-and-future-of-eye-treatment

Computational approaches have revolutionized how we interpret data. With the advent of genomic sequencing, scientists can derive significant conclusions from sequence data. For example, through transcriptomics – the study of genes and their expression in different cells – researchers have made groundbreaking discoveries in fields like developmental and disease biology. More recently, computational approaches have expanded with the introduction of generative artificial intelligence (AI) and its ability to generate new insights from massive datasets, diverse in scope, which can be validated in the lab. In this episode, co-host Maria Wilson sits down with John Marioni, Senior Vice President and Head of Computational Sciences, to discuss how computational methods can complement other research techniques to expedite drug discovery, enhance clinical trials, and prevent biases, ensuring the development of medicines that can treat people of diverse backgrounds. Read the full text transcript at www.gene.com/stories/merging-minds-and-machines-the-future-of-drug-discovery

Join Danielle Mandikian and Maria Wilson as they kick off season five of Two Scientists Walk Into a Bar. Hear about their recent lab adventures and enjoy a sneak preview of exciting topics for our new season. From demystifying the impact of AI and machine learning in drug development to exploring diverse modalities for treating diseases, we've got an exciting lineup in store. Subscribe today so you don't miss an episode! Read the full text transcript at: www.gene.com/stories/season-five-teaser

When we consider how a vaccine works, we typically think about vaccines that prevent infectious disease like flu or measles. But another type, known as therapeutic vaccines, may be able to treat diseases even after they've taken hold in the body – including cancer and viral infections. Similar to preventative vaccines, these therapeutic cancer vaccines work by promoting an immune response. Cancer vaccines are an emerging approach that have the potential to train the immune system to better seek out and destroy cancer cells. Co-host Danielle Mandikian sits down with Lélia Delamarre, Director and Distinguished Scientist, Cancer Immunology, and Ina Rhee, Executive Group Medical Director, Oncology Early Clinical Development, to discuss the fascinating science behind cancer vaccines as well as current challenges and opportunities. Read the full text transcript at https://www.gene.com/stories/learning-from-vaccines-training-our-immune-system-to-fight-cancer

Because disease outcomes and responses to treatment can vary across populations, clinical research must include patients who are racially, ethnically and gender representative of those who experience health conditions. Scientists are pioneering new ways of achieving inclusive and diverse clinical trials to generate clear results and reveal insights when evaluating new medicines. Co-host Maria Wilson sits down with Nicole Richie, Global Head of Health Equity and Population Science, and Jenn Pangilinan, Vice President, Genentech Research and Early Development (gRED) Clinical Operations, to discuss the nuances of human biological difference and how we can take a more thoughtful approach to diversity in clinical trials. This episode is the second in a two-part series dedicated to inclusivity and diversity in research. Read the full text transcript at www.gene.com/stories/representation-matters-inclusivity-in-clinical-trials

Achieving the first complete sequence of a human genome via the Human Genome Project represents an incredible feat – but it's just the tip of the iceberg when it comes to unlocking the power of genomics for drug discovery and development. As the scientific community builds on our understanding of genomics, one of the most critical questions becomes, how can we thoughtfully collect and use genetic data to better understand and support the health of all communities, especially those who have been excluded from research in the past? Co-host Maria Wilson sits down with Mark McCarthy, Principal Fellow and Executive Director of Human Genetics, to explore the interplay between genetics, research, and health equity – and the potential for more diverse genetic data to create a more equitable health landscape. This episode is the first in a two-part series dedicated to inclusivity and diversity in research. Read the full text transcript at: www.gene.com/stories/its-personal-inclusive-research-and-precision-medicine

Bacteria – and their constant ability to rapidly evolve and adapt – represent a scientific challenge that's equal parts fascinating and disconcerting. The incredible innovations of the past century have not only prevented and treated infections that would otherwise be lethal, but also helped safeguard patients through critical surgeries and other treatments. However, challenges abound for the scientific community when it comes to discovery and development of new antibiotics. Chief among these is antibiotic resistance, with more than 2.8 million antibiotic-resistant infections every year leading to over 35,000 deaths. Co-host Danielle Mandikian sits down with Michael Koehler, Principal Scientist, Discovery Chemistry, and Melicent Peck, Project Team Leader and Senior Medical Director, to explore how the field is combating the crisis of resistance through novel antibiotics and antimicrobial stewardship. Read the full text transcript at: www.gene.com/stories/antibiotic-resistance-a-call-to-arms. Note: There is a reference at 10:15 to an infected blister causing the death of Abraham Lincoln's son; it is actually Calvin Coolidge's son.

Understanding what happens in the brain is notoriously difficult, but scientists have made progress in the past few decades. For Alzheimer's disease, scientists have expanded their knowledge of where and when certain proteins, cells and biologic processes can contribute to memory loss and the progression of the disease. Co-host Maria Wilson speaks to Jasi Atwal, Senior Scientist, Neuroscience, and Edmond Teng, Senior Medical Director, to discuss the diverse theories and research approaches to Alzheimer's disease and how they are informing the development of potential new treatments. Read the full text transcript at www.gene.com/stories/the-where-and-when-of-alzheimers-disease.

Taking a deep breath can seem like a simple process; however, for millions of people with asthma, inflammation of the airways could make it difficult to breathe. While current treatments help manage symptoms, scientists are working to develop new therapies that target the underlying causes of the condition. Co-host Maria Wilson speaks to Jane Kenny, Senior Director and Senior Principal Scientist, Drug Metabolism & Pharmacokinetics, and Mark Wilson, Principal Scientist, Immunology Discovery, to learn more about the biology of asthma, the complexities behind inhaled drug delivery and how current research is informing the future of asthma care. Read the full text transcript at: www.gene.com/stories/take-a-deep-breath-treating-asthma

Our understanding of what causes multiple sclerosis (MS) has transformed over the last few decades. While discoveries of the cell types involved in MS progression — both immune and brain — have led to major advancements for patients, there is still much to learn. Co-host Danielle Mandikian speaks to Ann Herman, Senior Director and Senior Principal Scientist, OMNI-BD Inflammation and Infectious Disease, and Tracy Yuen, Senior Scientist and Biology Team Lead, Neuroscience, to learn more about ongoing research that may inform future therapies. Read the full text transcript at: www.gene.com/stories/demystifying-ms-the-intersection-of-immunology-and-neuroscience

Two Scientists Walk Into A Bar is back for a fourth season with new hosts, Maria Wilson and Danielle Mandikian! Get to know the new hosts and preview this season. Subscribe today so you don't miss an episode! Read the full text transcript at https://www.gene.com/stories/meet-the-hosts-of-season-four?topic=two-scientists-walk-into-a-bar

Cells are the basic unit of life, with a remarkable ability to sense their environment, process information and adapt accordingly. With 37.2 trillion cells in the human body, there remains plenty for scientists to discover about how this symphony of cells is organized and works together. In this special episode, producer Wellington Bowler chats with Aviv Regev, Executive Vice President, Genentech Research and Early Development, to discuss her vision for the roles that single cell genomics and computational biology can play in not only forwarding our basic understanding of biology, but also in our ability to generate new insights about disease and ultimately develop new medicines for patients.

The biological mysteries of age-related diseases have intrigued scientists for decades. In recent years, our expansive knowledge of genetics, thanks to the humble fruit fly, has opened our eyes to the mechanisms underlying these conditions. Now scientists are hoping to apply this knowledge to use the body’s own biological systems to delay the onset of disease or engage repair mechanisms once a disease has arisen. Jane speaks to Heinrich Jasper, Staff Scientist, Immunology Discovery, to learn more about the field of regenerative medicine and extending health.

In Season 1, we talked about using biomarkers and big data to match patients with the best treatment for their disease. In this episode, Jane sits down with David Shames, Senior Director of Cancer Immunotherapy Biomarkers and Staff Scientist in Oncology Biomarker Development, and Mark Lee, Senior Vice President and Global Head of Personalized Healthcare in Product Development, to discuss how a variety of big data approaches can be used to advance knowledge in real-time and aid in delivering more personalized care to patients. Tune in to find out why every scientist in the future just might need to be a data scientist too.

Our eyes are our windows to the world, but what happens when those windows start to fade or disappear? To understand how the eye works, scientists are combining developments in imaging and genetics to see into the eye and better understand why a disease occurs or whether a treatment is working. Hear from our host Jane Grogan and Menno van Lookeren Campagne, Principal Scientist, Immunology, and get a glimpse into how researchers are combining genetics, imaging and natural history data to better predict eye diseases like age-related macular degeneration and potentially treat them earlier. While Menno van Lookeren Campagne was an employee at the time this episode was recorded, he has since left Genentech.

It’s easy to think of cancer as an invader to the body. But in reality, it’s simply the result of a few proofreading errors in DNA replication that occur over time when cells divide. In Episode 3, Jane Grogan chats with Fred de Sauvage, Vice President and Staff Scientist, Molecular Oncology, about how just a handful of mutations can make normal cells go rogue, and how the field is finding new ways to stop the growth of cancer in its tracks.

Last episode, Jane and colleagues unraveled the intricacies of the human microbiome. This week, Jane chats with Mary Keir, Senior Scientist, Biomarker Discovery OMNI, to learn what happens during inflammatory bowel disease (IBD), what causes it, and how targeting dysfunction in our immune system, the gut epithelial barrier and our microbiome could reduce inflammation in the gut.

Our bodies are full of bacteria - pounds of them actually. We’re kicking off Season 3 with a closer look at the human microbiome and what happens when the synergistic relationship between our cells and our bacteria goes awry. Jane Grogan talks about the latest discoveries in microbiome research with Allyson Byrd, Associate Scientist, Cancer Immunology, Bioinformatics.

Two Scientists Walk Into a Bar is back for a third season with host Jane Grogan chatting with scientists who are leading the charge to understand complex diseases. This season will tackle a range of new topics, including a deep dive into the human microbiome, the latest in multiple sclerosis, asthma and aging, and how Big Data is redefining personalized healthcare. Subscribe today so you don’t miss an episode!

So far this season we’ve talked about the immune system a lot – how immune cells communicate, traffic along connective tissue, and invasive tumors. But what actually is the immune system? What’s it made of? How does it work? To close out our second season, Jane speaks with Andy Chan, Senior Vice President of Research Biology, to unravel the mysteries behind the immune system.

Pharmacology is the study of how a medicine works in the body, which is a critical step in understanding what medicines people should be given, and at what dose and schedule. As we learn more about the complex genomics that make each person unique, the role of pharmacologists is becoming increasingly important for personalizing safe and effective treatments. Jane speaks to Sara Kenkare-Mitra, Senior Vice President, Development Sciences, to get a glimpse into the future of this field.

Neurons, the cells that make up our brain, are some of the most unique cells in our bodies. The complex nature of how they communicate leads to everything we say, think, or do. That complexity makes it hard to correct neural communication when something goes wrong, as in neurodegenerative diseases. What can we do to fix that? Jane talks to Casper Hoogenraad, Senior Director and Staff Scientist in Neuroscience, to find out more.

The lifecycle of a cell mirrors our own lives – cells live and die as we do. It would be easy to think of cell death, or apoptosis, as a negative action, but the death of a cell is actually critical to many of the important biological functions that keep our bodies running. Learn more about the mysteries behind cell death from Vishva Dixit, M.D., Vice President, Physiological Chemistry.

Despite the best efforts of the human immune system, viruses and bacteria are constantly evolving to find new ways to breach our bodies’ natural defenses. Over the years, scientists have stepped in to develop novel ways to help the immune system in fighting infectious diseases. It’s a complicated field, which is why in this episode Jane is bringing in two scientists – Man Wah Tan, Senior Director and Principal Scientist, and Jorge Tavel, Group Medical Director, from the infectious disease team – to talk about where the field is headed.

Chemistry is all around us – from the air we breathe, to the food we eat, to the medicine we take when we’re sick. And for the researchers working to figure out how to make those medicines, chemistry can be an art as well as a science. Learn more as Jane talks to Wendy Young, Vice President, Discovery Chemistry.

The world of proteins is a minuscule and elegant ballet. Recent advances in imaging techniques have given us unprecedented views into this microscopic world, which could help us design better targeted therapies for a wide range of diseases. Learn more from Sarah Hymowitz, Vice President, Protein Sciences at Genentech, about why she has fallen in love with all things protein.

If your body was a city, then connective tissue would be the infrastructure tying everything together. It’s a hidden universe that helps many types of cells talk to each other and helps us fight diseases like rheumatoid arthritis or cancer. That’s why Shannon Turley has dedicated her research to uncovering the complexities of connective tissue, from her days as a graduate student shuttling ice boxes of live cells on the train to Principal Scientist of Cancer Immunology at Genentech. Hear more from Shannon on our debut episode of Season 2!

Jane Grogan and her producer Wellington Bowler are back for a second season of Two Scientists Walk Into a Bar. After a summer hiatus, Jane is eager to take on a new season of topics, including the 101 on proteins, infectious disease, how tumor microenvironments work and cell death. Subscribe today so you don’t miss an episode!

Designing a clinical trial is fascinatingly complex. There are dozens of variables that could influence the ability of any given trial to be successful. Navigating this complexity is truly a science unto itself. In our latest episode, Merdad Parsey, Senior Vice President of Early Clinical Development, explains how the science of clinical trial design has evolved, and where it’s headed.

Each person’s cancer is unique, so trying to match the right treatment to the right person is one of cancer biology’s biggest remaining challenges. In our latest episode, Priti Hegde, Director of Oncology Biomarker Development at Genentech, talks about how big data and advanced technology are guiding the future of personalized cancer immunotherapies.

Some types of breast cancer can become “addicted” to estrogen signaling, so treatments that target the estrogen receptor were once thought to be a magic bullet against this disease. But breast cancer is sneaky, and some mutations can allow it to sidestep these types of targeted therapies. In our latest episode, Lori Friedman, Senior Director of Translational Oncology at Genentech, talks about the ways scientists are trying to stay one step ahead of breast cancer.

Bacteria are remarkably fast shape-shifters. As soon as we develop new antibiotics against them, they mutate, leading to drug-resistant strains the world has never seen before. This could mean that one day we end up weaponless against an army of drug-resistant superbugs. But a new generation of “super antibiotics” could hold the key to overcoming this problem. Learn how as we sit down with Rick Brown, Vice President of Immunology and Infectious Diseases at Genentech, in our latest podcast.

In 1848 an explosion launched an iron rod through Phineas Gage’s brain. He miraculously survived, but wasn’t the same person, giving scientists the first clues into how neurodegeneration can affect what it means to be human. In our latest episode, we sit down with Geoff Kerchner to learn about the latest ways scientists are trying to halt the neurodegeneration seen in diseases like Alzheimer’s, Parkinson’s and ALS. As both a practicing neurologist and research scientist, Geoff gives us an inside peek at how his findings from the clinic can help unravel some of the most fundamental mysteries about the brain.

Communication is the key to good relationships. That’s true not only for people, but for our cells as well. If cellular communication goes wrong, your brain may stop processing information, or your organs might form tumors. So how do cells talk to each other? This week Jane Grogan sits down with Shiva Malek, whose work focuses on “eavesdropping” on the chatter between cells to understand what they’re saying and what goes wrong in a diseased state like cancer. We’re sure the cells don’t mind.

Pain is actually good for us. Until it’s not. Discovering how to fight chronic pain, while leaving acute pain intact, is no easy venture. Join Morgan Sheng as he takes us on a tour of the different pain systems in our body, and how a family of Pakistani street performers helped scientists identify a novel target for treatment.

A revolution in cancer care is happening right now. In our debut episode, Jane Grogan sits down with Ira Mellman, one of the world’s foremost experts in the field of cancer immunotherapy, about the “a-ha” moments that could mean the next breakthrough, from checkpoint inhibitors to cancer vaccines. Plus Ira waxes poetic about transitioning from a life of music to a life of science.

The only thing Jane Grogan loves more than doing science is talking about it. In addition to being an accomplished scientist leading research on inflammation, autoimmunity and tumor immunobiology, Jane has a background in radio. So when we decided to record our first podcast series — Two Scientists Walk Into A Bar — she was the natural choice to host. Subscribe today to learn what our top scientists are working on.