Conference Presentation
Programming Medicine
- The evolution of medicine has progressed from natural discovery to synthetic chemistry, biotechnology, and currently, the "programming" of living things as therapeutics.
- Ancient Egyptians used willow bark 2,500 years ago to treat pain; this remains the active ingredient in modern aspirin.
- Chemistry enabled the creation of novel molecules, establishing the lineage to the modern pharmaceutical industry.
- Recombinant DNA technology, discovered nearly 40 years ago, allowed for the bacterial production of complex molecules like insulin, overcoming the limitations of synthesizing them chemically.
- A paradigm shift is occurring where cells, genes, and microbes are no longer just targets of medicine but are engineered to serve as the medicine itself.
- This era involves programming living entities to sense disease, execute therapeutic programs, contain their actions, and self-terminate.
- Four specific programming imperatives are required for living medicines to function effectively as therapeutics.
- Sensing: The ability to detect environmental signals indicating the presence of disease.
- Execution: The capacity to run a predetermined program to address the detected condition.
- Containment: Mechanisms to restrict replication or movement to the specific site of disease.
- Termination: The ability to sense when a disease is alleviated and shut down or eliminate themselves.
- CAR-T therapy exemplifies current advancements in programming cells to treat cancer.
- First approved last year, it involves engineering a patient's immune cells to recognize and attack tumors.
- While showing high remission rates and cures, current applications are largely limited to leukemias.
- Future iterations aim to engineer T cells with sophisticated logic circuits (e.g., by portfolio company Asimov) to target a broader range of cancers and self-terminate after treatment.
- Gene therapy faces specific historical and technical challenges regarding safety and delivery.
- The field experienced a 20-year stagnation ("winter") following the 1999 death of Jesse Gelsinger due to a catastrophic immune response caused by a lack of containment.
- The first approved gene therapy last year targeted a rare form of blindness, partly because the eye is a well-contained organ with low risk of leakage.
- Future success relies on engineering viral vectors with low immune responses and high specificity to prevent off-target effects.
- Precision editing tools like CRISPR are being developed to repair specific mutations without affecting healthy genes.
- Microbiome therapies, or "bugs as drugs," are being engineered to replace metabolic functions within the body.
- A company named Synlogic is running a clinical trial for Phenylketonuria (PKU), engineering microbes to break down toxic amino acids that patients cannot process.
- Current strategies address safety by using microbes with short half-lives that self-eliminate after a few days.
- Future goals include programming bugs to remain inactive until inflammatory markers are detected and to include "kill switches" for manual or automatic elimination post-treatment.
- Approximately 40% of the audience is projected to be diagnosed with some form of cancer in their lifetime, driving the demand for advanced cell therapies.
- There are approximately 5,000 known diseases caused by single gene mutations, representing a large target for future gene therapies.
- The trajectory of medical development suggests that successive generations of living medicines will become increasingly sophisticated, effective, and applicable to a broader range of diseases.
- As these living medicines integrate into the human body, the speaker posits that we are "reprogramming ourselves" to achieve long-sought cures.