Dec 22, 2018 · 16m · a16z
Programming Medicine
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gold bands on the timeline = statements, start to end. Hover to read, click to jump. CC turns on captions
At the a16z Summit, Jorge Conde details the evolution of healthcare toward 'programming medicine,' where cells, genes, and microbes are engineered as living therapeutics. By incorporating synthetic biology control circuits—sensing, executing, containing, and terminating—these living drugs transition medicine from treating symptoms to delivering durable cures.
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 0.0 Guest teaching 5.7 Guest disagreement 0.0 The host pushing back 0.0
speaking balance: gold is the host, purple is the guest (3 minute bins)
Sharpest disagreement ▶ 10:25 Addressing Historical Gene Therapy Failure
In a non-combative keynote presentation, Conde speaks most starkly when highlighting the fatal containment error that halted gene therapy research for two decades.
Hardest push from the host ▶ 5:30 Audience Clarification InterjectionAn audience member briefly interrupts asking how drug development works, representing the only prompt during the presentation.
Biggest teaching moment ▶ 10:25 Jesse Gelsinger Clinical Trial AnalysisConde provides detailed educational context on the exact systemic immune response failure that reshaped gene therapy safety requirements.
The host holds their own ▶ 11:15 Ocular Gene Therapy RationaleConde demonstrates deep industry knowledge by explaining why blindness was targeted first due to the eye's natural biological containment.
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 |
|---|---|---|---|---|---|---|
| Era 1: Discovering Medicines in Nature | 0 | 5 | 0 | 0 | Jorge Conde provides a solo historical presentation on drug discovery, moving from willow bark to chemistry and recombinant DNA insulin. Because this is a monologue presentation without host interaction, host expertise and pushback are zero. | |
| The Paradigm Shift: Programming Living Medicines and ADMETox Framework | 0 | 6 | 0 | 0 | Conde introduces the paradigm shift toward living therapeutics and outlines the ADMETox framework for drug development. Aside from a brief audience prompt, there is no host participation. | |
| The Four Imperatives of Living Medicines: Sense, Execute, Contain, Terminate | 0 | 6 | 0 | 0 | Conde details the four imperatives of living medicines (sense, execute, contain, terminate) and highlights CAR-T therapy and gene logic circuits. | |
| Gene Therapy: Overcoming Containment Challenges with Engineering and CRISPR | 0 | 7 | 0 | 0 | Conde delivers an in-depth explanation of gene therapy history, citing the Jesse Gelsinger containment trial tragedy and modern CRISPR solutions. | |
| Microbe Therapy: Engineering the Microbiome and Kill Switches | 0 | 6 | 0 | 0 | Conde details microbiome engineering ('bugs as drugs') and concepts such as synthetic kill switches for terminating therapeutic bacteria. | |
| Conclusion: Building the Next Generation of Living Therapeutics | 0 | 4 | 0 | 0 | Conde concludes his presentation with an inspirational summary of how living therapeutics re-program human biology to achieve true cures. |
Statements from this episode (13)
Humans are increasingly able to program living things as medicine
“And specifically, I want to talk about our increasing ability to program living things to serve as medicines for us.”
Chemistry-based drug development faces fundamental limitations
“And so those chemistry based medicines have served us in countless ways to treat and manage disease, but there's a limitation to what we can do with chemistry. So beyond developing our own medicines, we had to find ways to produce medicines that we couldn't ma…”
Synthetic biology enables cells and genes to become medicines themselves
“But with advances in synthetic biology, advances in our ability to use things like gene and cell engineering, we're increasingly finding ways to make those same cells and genes and microbes, not the target of medicines, but the medicines themselves.”
Living therapeutics require sensing, execution, containment, and termination
“So there are four fundamental things that these living things need to be able to do well to act as therapeutics. The first one is they need to be able to sense their environment. They need to be able to look and search for the presence of disease. The second t…”
40% of people will receive a cancer diagnosis in their lifetime
“In the case of cancer, it's unfortunate that 40% of the men and women in this room will likely be diagnosed with a form of cancer somewhere in their lives, sometime in their lives.”
Approved CAR-T cell therapies are currently limited to leukemias
“But for the most part, today, this is limited to leukemias.”
Cell therapy's future depends on increasingly sophisticated cellular programming
“So the future of cell therapy Will depend on our ability to program with increasing sophistication cells to go after a broad range of cancers.”
Around 5,000 known diseases are caused by single-gene mutations
“So gene therapy has been the holy grail for treating the approximately 5000 known diseases that are caused by a single gene mutation.”
The first approved gene therapy treated a rare form of blindness
“And last year saw the approval of the first gene therapy for a treatment of a rare form of blindness.”
Precise editing and better delivery will expand gene therapy applications
“So as we advance our ability to deliver gene therapy, as we advance our ability to actually very precisely edit the genes, and only the genes that we need to edit, gene therapy will become applicable to a far broader range of diseases, not just limited to thos…”
Synlogic initiated the first clinical trial for an engineered microbe therapy
“And the first clinical trial to do this is already ongoing. A company called Synlogic has engineered a microbe that allows it to break down A, an amino acid in a disease called fetal, phenolketonuria, PKU, in patients that are unfortunately not able to break d…”
Controlling and terminating microbes is the primary challenge in living drugs
“Now, the problem with the microbiome therapies is that it's largely a termination question, is how do you ensure that this micro, this microbe that you've introduced to the body doesn't run amok, doesn't go out of control, and the way they've addressed that is…”