Ever since the discovery of antibiotics, microbiologists have worried about and studied how bacteria acquire resistance to these drugs. Adding to the complexity of this problem is the fact that it is not always clear whether the conditions that drive the evolution of resistance in the lab occur in patients suffering from bacterial infections. This is where the work of Nathalie Balaban -- Professor at the Hebrew University, and our guest on this episode -- comes in. The article we discuss is based on a foundation of research done in her laboratory, but this study makes the important step into the clinic by using samples from a patient with a life-threatening bacterial (MRSA) infection. By analyzing these patient samples, Dr. Balaban and her team were able to understand the conditions that lead to multi-drug resistance in a hospital setting. The work reveals how the ability of bacteria to enter a state of dormancy, also known as tolerance, can act as a stepping stone to resistance and can interfere with the efficacy of drug combinations. Our conversation covers what tolerance is, the conditions that promote tolerance, how it can lead to resistance and impact drug combination therapies, and lastly, integrating this new understanding into clinical microbiology protocols. "Effect of tolerance on the evolution of antibiotic resistance under drug combinations" in Science (January 2020) by Jiafeng Liu, Orit Gefen, Irine Ronin, Maskit Bar-Meir, Nathalie Q. Balaban. a16z bio Journal Club (part of the a16z Podcast), curates and covers recent advances from the scientific literature -- what papers we’re reading, and why they matter from our perspective at the intersection of biology & technology (for bio journal club). You can find all these episodes at a16z.com/journalclub.

Dr. Marty Makary—surgical oncologist at Johns Hopkins University School of Medicine, and health policy and innovation expert—has long been a passionate advocate for transparent pricing in the healthcare system. We don’t talk enough (or really at all) about price in healthcare, says Makary (instead, we talk about cost). But shedding a light on prices in healthcare—from not just what those prices are but how prices are set and the value we all receive as consumers of the system overall—can help us measure quality in medicine, and be a driver for real behavioral change in the healthcare system, correcting many of the unintended consequences of a fee-for-service system like surprise billing or unnecessary medical procedures. In this conversation with a16z General Partner Julie Yoo, Makary and Yoo discuss what price transparency in the healthcare system could really do; how we can "steer" towards the good physicians who are not just highly skilled, but make the right judgment calls based on need and holistic health, not cost; how we might distinguish between high value and low value through medical appropriateness; and how we might gain clinical wisdom from other kinds of scientific discovery beyond randomized controls, especially during the wartime protocol of COVID-19.