Jan 2, 2019 · 28m · a16z
a16z Podcast | Mindsets for Engineering Biology
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gold bands on the timeline = statements, start to end. Hover to read, click to jump. CC turns on captions
In this episode of the a16z podcast, host Hannah, MIT Professor Bob Langer, and a16z General Partner Vijay Pande discuss how biological science is transitioning into a programmable engineering discipline. They explore historical paradigm shifts in biomaterials and drug delivery, the interplay between high-throughput automation and rational design, and strategies for biotech translation and regulatory navigation.
How this conversation actually went
Every chapter scored 0–10 on four independent dynamics. Hover any point for the reasoning behind the score. How this is scored →
The host as informed peer 2.9 Guest teaching 5.6 Guest disagreement 1.0 The host pushing back 0.9
speaking balance: gold is the host, purple is the guest (3 minute bins)
Sharpest disagreement ▶ 13:10 Philosophical pushback on high-throughput empirical methods
Vijay explicitly pushes back against relying solely on high-throughput brute-force screening, framing it as an unideal pre-industrial approach compared to rational engineering principles.
Hardest push from the host ▶ 14:26 Host pressing on domain selection for design vs discoveryHannah actively intervenes in the debate between Vijay and Bob to ask precisely how one determines which biological problems are ripe for rational design versus empirical discovery.
Biggest teaching moment ▶ 1:11 Girdle material used in artificial heartsBob Langer educates the host with a surprising historical fact: early artificial hearts used polyether urethane sourced directly from ladies' girdles, establishing how haphazard biomaterial selection used to be.
The host holds their own ▶ 23:35 Deconstructing the Hippocratic Oath in modern bio-regulationVijay Pande demonstrates high-level domain expertise by reframing regulatory bottlenecks around the 'do no harm' principle, calling for a shift toward optimizing population health rather than ancient Greek risk-aversion.
the scores for every segment, with the reasoning behind each
| Chapter | Topic | The host as informed peer | Guest teaching | Guest disagreement | The host pushing back | Why |
|---|---|---|---|---|---|---|
| Historical Paradigm Shifts in Biomaterials | 2 | 5 | 1 | 1 | Host Hannah asks conversational introductory questions and reacts with awe at Langer's historical anecdotes regarding biomaterials. Langer educates the room on how early clinicians used household items like ladies' girdles and mattress stuffing for artificial hearts and implants due to regulatory inertia. | |
| Breakthroughs in Targeted Drug Delivery and Controlled Release | 3 | 6 | 0 | 1 | Hannah facilitates with simple clarifying prompts like 'Slow release, basically?' while Langer and Vijay detail drug delivery systems. Langer explains how microspheres and local delivery mechanisms like drug-eluting stents alter drug safety profiles. | |
| The Evolution of Biopharma: From Proteins to Genetic Therapeutics | 2 | 6 | 0 | 0 | Langer presents an educational breakdown comparing protein, DNA, and RNA therapeutics, highlighting delivery challenges to the nucleus versus cytoplasm. The dynamic is purely informative and collaborative without host pushback. | |
| High-Throughput Automation vs. Rational Engineering | 4 | 6 | 3 | 2 | Vijay offers a mild contrarian perspective by expressing a love-hate relationship with high-throughput methods, favoring rational engineering over brute-force screening. Hannah prompts the guests effectively to delineate which areas suit rational design versus empirical crunching. | |
| Translational Research, Academia, and Startup Dynamics | 3 | 5 | 0 | 1 | Hannah asks an insightful question about the mindset shift required between academic discovery and industrial engineering. Langer and Vijay elaborate on how academic culture has shifted toward translation over the past three decades. | |
| Navigating Regulation: Balancing Safety with Medical Innovation | 4 | 6 | 3 | 1 | Langer explains historical FDA pivots following the AIDS epidemic and the Vioxx withdrawal. Vijay introduces a philosophical challenge to the ancient Hippocratic Oath's 'do no harm' mandate, arguing modern healthcare regulation should optimize for public health benefit. | |
| Future Horizons: Cell Therapies, Regenerative Medicine, and Healthspan | 2 | 5 | 0 | 0 | The conversation concludes with forward-looking statements on regenerative medicine and organ synthesis. Langer outlines his vision for organ-on-a-dish technology to eliminate animal testing, while Vijay notes the challenge of translating multi-omic readings into action. |
Statements from this episode (11)
Langer: Artificial hearts still use ladies' girdle material after 50 years
“If you wanted to make an artificial heart, what the clinicians did in 1967 is they said, well, what object in your house has a good flex life like a heart? And they came up with the idea of a lady's girdle. So they looked at what that was made out of, and It's…”
Langer: Breast implants rely on mattress stuffing and silicone lubricant
“That's still one of the two main breast implant materials. One is a mattress stuffing, and the other is actually a lubricant, which is silicone.”
Langer: Nucleic acid therapeutics will fail without targeted delivery
“And these, I think delivery ends up being so critical because if you can't deliver them, you know, probably those drugs will not work.”
Langer: Local delivery via stents cuts systemic drug doses by 1,000x
“The systemic dose is maybe one 1000th of what it would be as if you swallowed it. So by delivering locally, you can totally change the safety and dosage profile.”
Langer: Seven of Top 10 Best-Selling Drugs Are Protein Biologics
“If you look at the top 10 selling best drugs in, you know, this past year, seven of them were protein, are protein drugs. If you looked at it even 15 years ago, at best it would have been one, but now that's really the majority. And the sales are over two hund…”
Langer: High-throughput screening solved Abbott's Norvir crystal crisis in two weeks
“Now, seven years later, what we did is, just in two weeks, using this high-throughput approach, not only created crystal form two, which is where they were when they stopped, but we also created crystal form one and discovered three new crystal forms that had …”
Pande: Biological engineering requires predictive accuracy, not 100,000 empirical guesses
“It's all about, can you make predictions? So if you think you can engineer something, you should be able to make 10 predictions and have three work, not making a 100,000 guesses and seeing what pans out.”
Langer: Academic involvement in startups was frowned upon in the 1980s
“If I go back to when I started, you know, doing this in the, you know, early eighties, that I think in academia, it was somewhat frowned upon. Of getting involved with very translational work and applied work in companies. And I don't think that that's, and I …”
Langer: Withdrawing Vioxx from the market in 2005 was wrong
“The second one that I think had a negative effect was the Vioxx situation in 2005, and, you know, there was just a small increase in deaths with this drug, but there were so many lawsuits over it, That people at the FDA would get called on the carpet for appro…”
Pande: FDA approval requires specific disease indications over general longevity
“You probably couldn't even get it through FDA if you didn't have an indication, like staying healthy longer was not an indication.”
Pande: Longevity therapeutics will focus on extending healthspan, not lifespan
“We're going to start to see drugs, and some of them are associated with what we see people talking about with longevity, but really it's not about living longer, it's about just pushing back those problems further and further. Such that we have a longer, longe…”