# Genetic Engineering

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Category: Future
Slides: 14
Updated: 2026-05-17T20:51:50.237Z
Tags: future, genetic, engineering

## Summary

In one decade, gene editing went from Nobel-winning curiosity to FDA-approved cure. The next decade will decide what we are willing to do with the tools — and what we should refuse. Key sections include: Read. Write. Edit.; Three generations of editing; How a guide RNA finds a single base in 3 billion; What edits exist as medicine; The malaria question; The He Jiankui line; Beyond editing — designing genomes; Programmable life, in pieces; Cost of reading and writing DNA; Dual-use is the central problem.

## Slide Outline

1. Read. Write. Edit.
2. Three generations of editing
3. How a guide RNA finds a single base in 3 billion
4. What edits exist as medicine
5. The malaria question
6. The He Jiankui line
7. Beyond editing — designing genomes
8. Programmable life, in pieces
9. Cost of reading and writing DNA
10. Dual-use is the central problem
11. Who is shaping this
12. Recommended source
13. What stays speculative
14. Indicators · 2026–2030

## Slide Transcript

### Slide 1: Read. Write. Edit.

- Volume 6 · File 06
- In one decade, gene editing went from Nobel-winning curiosity to FDA-approved cure. The next decade will decide what we are willing to do with the tools — and what we should refuse.

### Slide 2: Three generations of editing

- §1 · Toolbox
- Gen 1 · 1990s
- ZFNs · TALENs
- Custom protein scaffolds; tedious to design, expensive. First germline-edit-of-a-disease tools.
- Gen 2 · 2012–
- CRISPR-Cas9
- Doudna & Charpentier (Nobel 2020). RNA-guided, cheap, programmable. Off-target effects manageable.
- Gen 3 · 2016–
- Base & prime editors
- Liu lab (Broad). Single-letter rewrites without double-strand breaks. Higher precision, lower toxicity.
- What's coming
- Epigenetic editing (CRISPRoff, Weissman 2021) — heritable expression change without DNA edit
- RNA editing (ADAR, RESCUE) — reversible, no germline footprint
- Programmable retroelements / bridge RNAs (Arc Institute, 2024)

### Slide 3: How a guide RNA finds a single base in 3 billion

- §2 · CRISPR · Diagram
- After Doudna & Charpentier 2012; Liu base-editor 2016; prime-editor 2019.

### Slide 4: What edits exist as medicine

- §3 · Approved & in clinic
- TherapyTargetStageYear
- Casgevy (exa-cel)Sickle-cell & β-thalassemia · BCL11A KO ex vivoFDA, EMA, MHRA approved2023
- Lyfgenia · bb305Sickle-cell · gene addition (lentivirus)FDA approved2023
- HemgenixHemophilia B · AAV gene therapyFDA approved · $3.5M list2022
- Verve VERVE-101HeFH · in vivo base edit of PCSK9Phase 1b2023–
- NTLA-2001ATTR amyloidosis · in vivo Cas9Phase 32024–
- Editas EDIT-301Sickle-cell · γ-globin reactivationPhase 1/22024–
- Beam BEAM-101Sickle-cell · base editingPhase 1/22024–
- forecast By 2030 we expect 10–20 approved gene-edit therapies, mostly for monogenic diseases. Polygenic disease editing remains experimental.

### Slide 5: The malaria question

- §4 · Gene drives
- Gene drives bias inheritance so an engineered allele spreads faster than Mendelian rates. Anopheles-suppressing drives (Target Malaria, Imperial College, Crisanti lab) crashed caged populations to extinction in Italian biocontainment by 2018. The technical question is solved. The ethical and regulatory question — release into the wild — is not.
- The hard questions
- Reversibility. Daisy drives (Esvelt, MIT) are designed to die out, but unproven at scale.
- Consent. Mosquitoes don't respect borders. Whose democratic process governs?
- Ecological cascade. Anopheles isn't a keystone species, but absence-of-evidence isn't evidence-of-absence.
- Dual use. The same toolkit could target useful insects.
- scenario First open-environment release likely 2027–32 in Burkina Faso or São Tomé, after Phase 4-equivalent safety review.

### Slide 6: The He Jiankui line

- §5 · Germline
- In November 2018, He Jiankui announced he had edited the CCR5 gene in human embryos that were carried to term — twin girls Lulu and Nana. The announcement provoked global condemnation, He's imprisonment (released 2022), and a near-universal moratorium on germline editing in clinic.
- The science: the edits were imprecise, the rationale (HIV resistance) thin, the consent forms misleading. The episode established the international norm: germline editing is technically possible, currently irresponsible, and not (yet) ethically supportable.
- The five accepted reasons
- Off-target risks not fully characterized
- Mosaicism — embryo-stage edits don't distribute uniformly
- Long-term inheritance unknown — multi-generational
- Less risky alternatives (PGT-M, IVF selection) exist
- Equity/eugenic concerns at population scale
- contested The line will be tested again — likely first by a wealthy parent with a Mendelian-disease child, in a permissive jurisdiction.

### Slide 7: Beyond editing — designing genomes

- §6 · Synthetic biology
- Synthetic biology asks: what if we wrote genomes from scratch? Craig Venter's JCVI synthesized Mycoplasma laboratorium in 2010; Sc2.0 (Boeke et al.) wrote the entire yeast genome by 2024. The toolkit:
- DNA synthesis
- ~$0.05/bp
- Twist, IDT, Ansa Bio. Down 1000× since 2003.
- Standard parts
- Registry of BioBricks
- iGEM (MIT) since 2003. Modular promoters, RBSes, terminators.
- Cell-free systems
- PURE · TXTL
- Run synthetic circuits without a cell. Liu, Murray labs.
- Genome writers
- Sc2.0 · synGenomes
- Designer chromosomes, refactored codes (Church Mb-scale).

### Slide 8: Programmable life, in pieces

- §7 · Xenobots & living machines
- Bongard, Levin & Blackiston (2020): "xenobots" — assemblies of frog skin and cardiac cells, evolved in silico, that swim, push pellets, and self-replicate by kinematic assembly. Not a normal organism. Not a robot. Some new category we don't yet have a word for.
- Anthrobots (Levin lab, 2023) — multi-cellular structures from human tracheal cells. Show neural-tissue repair effects in vitro.
- scenario Living therapeutics — engineered consortia for the gut, the wound bed, the bloodstream — are a more tractable near-term application than xenobots themselves.

### Slide 9: Cost of reading and writing DNA

- §8 · Diagram · S-curve
- After NHGRI sequencing-cost data; Carlson curves; Twist Bio & Ansa Bio reports. Schematic.

### Slide 10: Dual-use is the central problem

- §9 · Biosecurity
- Drexler in 1986 worried about gray goo. The contemporary worry is more specific: cheap DNA synthesis, available pathogen sequences, and AI-assisted protein design lower the bar to engineering pandemic-class agents. Kevin Esvelt's papers (2017, 2022) lay out the case bluntly.
- Synthesis screening. IGSC member companies screen orders against hazardous-sequence databases. Coverage is partial.
- Information hazards. Some research (gain-of-function, certain pandemic-pathogen sequences) may be unsafe to publish.
- AI uplift. Frontier labs evaluate whether models offer non-trivial uplift to bioweapon synthesis. Anthropic, OpenAI, DeepMind have biorisk evals.
- Hardware. Benchtop synthesizers will eventually be cheap enough that screening at the order step matters more than at the user step.
- "The scariest thing about pandemic-grade biotechnology is how few people it takes." — Kevin Esvelt

### Slide 11: Who is shaping this

- §10 · Voices
- Jennifer DoudnaBerkeley · CRISPR co-discoverer · Innovative Genomics Institute
- Emmanuelle CharpentierMax Planck Berlin · co-Nobel 2020
- Feng ZhangBroad · CRISPR mammalian use; bridge RNAs (Arc, 2024)
- David LiuBroad · base & prime editing
- George ChurchHarvard · Genome Project Write; mammoth de-extinction (Colossal)
- Kevin EsveltMIT · gene drives, biosecurity, daisy drives
- Michael LevinTufts · xenobots, basal cognition
- Eric DrexlerEngines of Creation (1986); molecular nanotech ground theorist
- Françoise BaylisBioethicist · germline-editing critic; Altered Inheritance (2019)

### Slide 12: Recommended source

- §11 · Watch
- Kurzgesagt · "Genetic Engineering Will Change Everything Forever"
- The 2016 video that introduced CRISPR to ~30M viewers. Aged remarkably well.
- youtube.com/@kurzgesagt →
- Lex Fridman × Jennifer Doudna
- Hour-plus on origins, ethics, the Broad-Berkeley patent fight, and where the science is going.
- youtube.com/@lexfridman →

### Slide 13: What stays speculative

- §12 · Frontier · 2050
- Polygenic enhancement. Embryo selection is shipping; effect sizes are small. Editing 100s of variants in vivo, safely, is decades away. scenario
- Mammoth / thylacine de-extinction. Colossal Biosciences has cells, edit pipelines, and elephant surrogates. First mammoth-elephant hybrid maybe 2028. scenario
- Synthetic genomes for production hosts. Sc2.0 finishes; bacterial chassis with refactored genetic codes deployed in industry. forecast
- Programmable cell therapies. CAR-T 4.0; in vivo CAR generators; logic-gated kill switches. forecast
- Designer babies, mass scale. Implausible without a major regulatory shift. fiction-adjacent

### Slide 14: Indicators · 2026–2030

- §13 · What to watch
- First in-vivo base-edit therapy approval (Verve, Beam)
- Open-environment gene drive trial
- Outcome of WHO & UNESCO heritable-genome-editing reviews
- Synthesis-screening federal mandate (US Executive Order 14110 successor)
- Sc2.0 yeast complete; commercial deployment
- First polygenic embryo selection birth-cohort outcome data (5+ yr)


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