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a16z Podcast | Mindsets for Engineering Biology
23 segments available
Head of the largest bioengineering lab in the world, former chairman of the FDA and one of the few recipients of the National Medals of Science and of Technology and Innovation, Bob Langer's work has spanned multiple fields and settings and has been applied across numerous fields, from pharmaceutical to chemical, biotechnology to medical device companies. What does it mean to move across disciplines like this, from science to engineering, both in the lab and into the field? In this conversation with general partner and head of the a16z bio fund Vijay Pande (with Hanne Tidnam), Langer and Pande share the challenges and opportunities as people move across different disciplines, as well as the changing mindsets for innovation as applied to biotech: first principles, "rational" biology, do no harm, and others.
Segments Timeline
Introduction to Bioengineering Mindsets
In this episode of the a16z podcast, Hanne Tidnam introduces a conversation about the intersection of science and engineering in bioengineering. The discussion features Bob Langer, a leading figure in the field, and Vijay Pande, who heads the a16z bio fund. They explore the challenges and opportunities that arise when moving across disciplines in biotechnology.
"hi everyone welcome to the a 16z podcast I'm Hana and today's episode continues our ongoing series on how science becomes engineering and all the new challenges and opportunities that presents as peop..."
Innovative Problem Solving in Medicine
Bob Langer shares insights on how clinicians historically approached medical problems using everyday materials. He recounts the story of how the first artificial heart was created using a ladies girdle material, highlighting the challenges of using non-optimal materials in medical devices and the implications for patient safety.
"conversation between a 16-0 partner Vijay Pandey who heads up our bio Fund and Bob Langer Institute professor at MIT whose work has really been all about the interface of engineering and materials in ..."
The Evolution of Biomaterials
Langer discusses the historical reliance on off-the-shelf materials for medical applications, such as breast implants made from mattress stuffing. He emphasizes the need for a paradigm shift in biomaterials, advocating for a more scientific approach to material selection that prioritizes optimal properties for medical use.
"if you want to make artificial heart what the clinicians did in 1967 is they said what object in your house has a good flex life like a heart and they came up with the idea of a ladies girdle so they ..."
Controlled-Release Systems Breakthrough
Langer describes his early work on controlled-release polymer systems for delivering large molecules like peptides and proteins. He explains how these innovations have transformed treatment options for conditions like prostate cancer and diabetes, allowing for sustained drug release and improved patient outcomes.
"are they the way most decisions used to be made for these kinds of materials or it was there was there no sense of choosing optimal material first or was it always sort of happenstance for most of the..."
Challenges in Drug Delivery
The conversation shifts to the critical importance of drug delivery systems. Langer and Pande discuss how effective delivery mechanisms can enhance the efficacy of drugs, particularly for large molecules that face absorption challenges. They highlight the need for innovative solutions to ensure drugs reach their intended targets.
"shift well that's actually right in fact when a lot of the material just the science departments were you know really aimed at totally different kinds of materials I'd love to hear some of your discov..."
Personalizing Medicine Through Targeted Delivery
Langer and Pande explore the concept of personalized medicine, emphasizing the potential of localized drug delivery systems. They discuss how targeted approaches can significantly reduce systemic side effects and improve treatment efficacy, drawing parallels to advancements in drug-eluting stents.
"they're put in these microspheres you can give them an injection and they can last for a month now even six months and that's led to new ways of treating prostate cancer and Dmitri OSIS type 2 diabete..."
The Future of Genetic Engineering
The discussion concludes with a look at the future of genetic engineering and its implications for drug development. Langer highlights the potential of DNA and RNA therapies to address genetic disorders, emphasizing the transformative impact these technologies could have on the pharmaceutical industry.
"just said if you try to take those drugs like taxall and give the amount that you needed systemic all over the body you take it orally or some other ways I mean it would probably kill somebody but but..."
The Future of Genetic Engineering
In this segment, Langer explores the potential of DNA and RNA drugs as the next frontier in genetic engineering. He discusses how advancements in gene therapy and gene editing could address diseases at their source, offering new hope for conditions like enzyme deficiencies.
"where the problems might occur so DNA say somebody has an enzyme deficiency disease gachet's disease as an example it took years to come up with the drugs that could help that you might do DNA therapy..."
Challenges of DNA Delivery
Langer explains the complexities involved in delivering DNA therapies, emphasizing the need to target the nucleus of cells. He contrasts this with RNA therapies, which can be more straightforward to administer, highlighting the advantages of RNA in treating genetic disorders.
"over proteins that you can make the you know it's you don't have to spend nine months to a year to manufacture the protein and and also the you don't have the challenge of protecting the protein all t..."
High Throughput Revolution in Drug Development
Langer shares insights on how high throughput methods are revolutionizing drug development. He recounts a case study of Abbott's AIDS drug, illustrating how modern technologies can solve complex problems in days rather than years, showcasing the power of automation in biopharma.
"name yet it's maybe technology in an via or something like that Bob how are you starting to see technological advances like machine learning or robotics affect how this kind of research in the bio spa..."
The Love-Hate of High Throughput Methods
Pande discusses the philosophical implications of high throughput methods in biology. He raises questions about the balance between empirical experimentation and rational engineering, emphasizing the need for a thoughtful approach in navigating the complexities of biological systems.
"appropriately the FDA because it changed told them it became a different thing exactly exactly and so the FDA told them to pull it off the market and so they did yet even after a long time years they ..."
Rational Engineering vs. Empirical Discovery
In this segment, Pande and Langer debate the merits of rational engineering versus empirical discovery in biological research. They explore how advancements in data analysis can inform predictions and improve the efficiency of drug development processes.
"have kind of a love-hate relationship with high throughput methods the love part you know as everything Bob mentioned is spot-on and you know and you've seen in other spaces like in protein crystallog..."
Leveraging Data for Drug Discovery
Langer and Pande conclude by discussing the importance of leveraging data in drug discovery. They highlight how high throughput screening combined with rational design can enhance the efficiency of identifying viable drug candidates, ultimately pushing the boundaries of biopharmaceutical innovation.
"out right people in synthetic biology are really pushing the envelope for what you can do in this sort of designed predicted engineering way and so I think it's a mistake to think that you know we can..."
The Shift from Science to Engineering in Biology
Langer reflects on the evolving landscape of biology, where engineering principles are increasingly applied. He discusses the differences between academic research and industry focus, noting how engineering is becoming more prominent in biological applications, leading to new opportunities for innovation.
"that might be valuable we often look at what should be done we're so questions where there's fundamental science that needs to be done academia is fantastic for that on the other hand questions that a..."
Challenges in Translating Research to Products
This segment addresses the challenges faced when transitioning from academic research to product development in the biotech industry. Langer shares insights on the importance of collaboration and the potential pitfalls that can arise during this handoff, emphasizing the need for a smooth transition to bring transformative products to market.
"this case of academia you're often trying to you know invent things or discover things but you don't necessarily need to have a product in ten years or 20 years or ever but but if you've learned some ..."
The Role of Academia in Translational Research
Langer discusses the evolving role of academia in translational research, highlighting the increasing acceptance of applied work. He notes the importance of basic research in driving innovation and the growing number of startups emerging from academic discoveries, showcasing the synergy between research and engineering.
"they can sort of get out the gate and and almost build startups enough sort of a fundamentally different way than you would maybe thirty years ago what happens in academia is you can you know make som..."
Navigating Regulatory Challenges in Biotech
In this segment, Langer shares his experiences with regulatory processes, particularly in light of historical events like the AIDS epidemic and the Vioxx situation. He discusses the balance between ensuring safety and the urgency of bringing effective treatments to patients, highlighting the complexities of regulatory decision-making.
"do you see that handoff happening now is it a smooth process or is there still a lot of challenge and a lot of opportunities for mistakes and failure I like to think that when we do it it's it's reaso..."
The Impact of Regulatory History on Innovation
Langer reflects on how past regulatory challenges have shaped current practices in the biotech industry. He emphasizes the need for a thoughtful approach to regulation that considers both patient safety and the necessity of timely access to innovative therapies, illustrating the ongoing tension in the regulatory landscape.
"different mindset and now is the mindset shift kind of the difference between discovery to engineering at heart what's the mindset shift actually and sort of pure research you know there's an Einstein..."
Regulatory Challenges in Biotech
Langer shares pivotal moments in FDA regulation, particularly during the AIDS epidemic and the Vioxx controversy. He explores the balance between ensuring safety and expediting drug approvals, emphasizing the need for a nuanced approach to regulation that considers both patient safety and the urgency of treatment.
"billions of dollars I'd love to shift gears a little bit and talk a bit about regulation having worked on the FDA science board the more than as is chairman and then also you know having been involved..."
Rethinking the Hippocratic Oath
In this segment, Langer critiques the traditional Hippocratic Oath of 'do no harm' in the context of modern medicine. He argues for a broader perspective that prioritizes optimizing health outcomes and encourages a reevaluation of healthcare practices to better serve populations.
"suffering on the other it's interesting that this concept of the Hippocratic oath that we want to do no harm is the guiding principle versus doing the most good and and I think do no harm make sense i..."
Advice for Startups on Regulation
Langer provides insights for biotech startups on the importance of considering regulatory pathways early in their development. He shares examples from his own experiences, illustrating how strategic planning can facilitate faster clinical trials and successful product launches.
"prevention that it's an exciting time when we even just really fundamentally rethink how we can help people the most what advice would you have for startups as they start to think about when do you st..."
The Future of Personalized Medicine
Langer discusses the transformative potential of genetic and regenerative medicine over the next two decades. He highlights the shift towards personalized therapies and the importance of addressing health issues proactively rather than reactively, aiming for a healthier aging process.
"you think will fundamentally change in the next 20 years and how we think about health care or medical treatment or even the way we do science I mentioned genetic medicines more personalized kinds of ..."
Innovations in Tissue Engineering
In this segment, Langer envisions a future where bioengineering can create tissues and organs for patient treatment, revolutionizing drug testing and minimizing animal testing. He emphasizes the importance of understanding complex biological systems and the challenges that come with new technologies in the field.
"to see solved that credit crashed in the next era being able to make virtually any tissue or organ that to help patients and also the other aspect of that is that it could could revolutionize drug tes..."