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Last Updated: 25.05.23

Siddhartha Mukherjee: History of the Cell, Cell Therapy, Gene Therapy

Attia hosts Siddhartha Mukherjee, an oncologist and Pulitzer Prize-​​winning author, discussing his book, The Song of the Cell. Siddhartha covers cell discovery, medical impact, evolution to multicellularity, cell-​​based therapies, gene therapy including CRISPR, ethical concerns, medical science challenges, the human brain, learning styles, writing process, and mental health.

Key Takeaways

High level takeaways from the episode.

CAR T‑cells: a special example of gene therapy

  • Extract T‑cells from a cancer patient
  • Use gene therapy to weaponize T‑cells to attack cancer cells
  • Reinject weaponized T‑cells into the patient
  • Successful in blood cancers like lymphoma, leukemia, and myeloma
  • Not as successful in solid tumors

Reasons for high cost of CAR T‑cell therapy in the United States:

  • High failure rate of drugs, pharmaceutical companies recoup R&D costs
  • CAR T‑cells are intrinsically expensive to make
  • Quality control and sterile environment required for production

Cost reduction strategies in India:

  • Cheaper virus production
  • Reduced patent burden
  • Changed machinery and cell harvesting methods
  • Lower hospital treatment and therapy costs

Three approaches to gene therapy for sickle cell anemia:

  1. Express the corrected version of the Betaglobin gene
  2. Use gene editing technology (e.g., CRISPR) to change the gene back to its normal form
  3. Reactivate fetal hemoglobin in adults to correct the hemoglobin defect

All three approaches are in trials and have shown various measures of success

CRISPR allows for precise changes in the human genome

  • Derived from a bacterial system evolved millions of years ago
  • Can delete or change specific words in the “library” of the human genome
  • Has the potential to revolutionize gene therapy and genetic editing

CRISPR technology allows for precise gene editing

  • Can change specific genes to their normal or wild type versions
  • Can be done with embryonic cells, stem cells, bone marrow cells, and T cells

Drawing the line between ethical and unethical gene editing

  • Huntington’s disease: high penetrance, devastating effects, altering embryos could be seen as ethical
  • APOE4 gene: risk factor for Alzheimer’s disease, but not as penetrant as Huntington’s, raises questions about where to draw the line

Distinction between disease and desire

  • Disease is linked to human suffering
  • Desire is the aspiration to ameliorate suffering, even when there’s no suffering involved

Genetic editing raises ethical questions on disease vs. desire

  • Enhancing intelligence or physical traits falls under desire

Mental health is a complex area for genetic editing

  • Autism and schizophrenia have genetic components
  • Simplifying these conditions could have unintended consequences

Two types of genes related to mental health:

  • Shove genes: strongly push towards a specific outcome (e.g., Marfan syndrome)
  • Nudge genes: small influences that accumulate (e.g., height)

Most mental illnesses are influenced by nudge genes

  • Difficult to change hundreds or thousands of genes at once


We recommend using this distillation as a supplemental resource to the source material.

  • Siddhartha Mukherjee: History of the Cell, Cell Therapy, Gene Therapy

    Attia The Drive #244

    Attia hosts Siddhartha Mukherjee, an oncologist and Pulitzer Prize-​​winning author, discussing his book on cell discovery, medical impact, and gene therapy.

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