TheFuture ofReproductiveTechnology:Therapy,Editing, orDesign?

Episode 5 ·MAPASGEN

Level: expert ·Topic: reproductive technology, bioethics, genome editing

In 2018,Chinese scientistHeJiankui announced that he had created the world's first genetically edited humans — twin girls whose embryos he had edited usingCRISPR-Cas9 to modify theCCR5 gene.His stated goal was medical: to reduce the risk ofHIV infection.The global scientific community's reaction was near-unanimous condemnation.He was sentenced to three years in prison.But the question he raised has not gone away: where does the line fall between treatment and design?

Part 1.AMap ofTechnologies:WhatExistsToday

Reproductive technologies with a genetic component form a spectrum — from well-established and legally permitted to experimental and prohibited almost everywhere.

Level 1.The standard —PGT (preimplantation genetic testing)

Used inIVF for more than 30 years.An embryo at the 5–6 day stage is biopsied — a few cells are analysed for chromosomal abnormalities (PGT-A) or specific mutations (PGT-M).Embryos without detected abnormalities are selected.The technology does not modify the genome — it only selects from what already exists.

Legal status: permitted in most developed countries.

Level 2.The frontier — mitochondrial donation

Described in detail in thePRO material.As of 2025, legalised in theUnitedKingdom andAustralia.Permitted within clinical research in several other countries.Modifies the mitochondrial genome (0.1% ofDNA) but not the nuclear genome.

The key issue: the changes are passed to the child's descendants through the maternal line.This is the first technology in history to create heritable genetic changes in humans that has received legal approval.

Level 3.Experimental — germline editing (CRISPR)

Modification of the nuclear genome of an embryo using molecular tools (CRISPR-Cas9 and its variants).UnlikePGT, which selects, editing creates a newDNA sequence that did not exist in either parent.

Legal status: prohibited for clinical use in almost all countries.For scientific purposes, permitted with restrictions in a small number of jurisdictions (China, theUK, theUS — only up to day 14 of embryo development).

Why it is prohibited: the technology is imperfect.Off-target effects — unintended changes to other parts of the genome — remain a significant risk.Additionally, the changes are inherited by all descendants, creating irreversible consequences for the gene pool.

Part 2.TheHeJiankuiCase:WhatWentWrong

The story ofHeJiankui is not simply a story about breaking rules.It is a story about how medical logic without ethical oversight leads to catastrophic decisions.

His reasoning appeared medical: the twins' father wasHIV-positive.TheCCR5 gene encodes a protein through whichHIV enters immune cells.People with a natural deletion inCCR5 (roughly 1% ofEuropeans) are resistant to certainHIV strains.The logic: editCCR5, protect the children fromHIV.

The problemsHe ignored:

1. The risk was not justified. Modern antiretroviral therapy reduces the risk ofHIV transmission from father to child to virtually zero.Genetic editing was simply unnecessary for this purpose.
2. TheCCR5 deletion is not harmless. Research shows that carriers of theCCR5 deletion have increased vulnerability to certain other viruses — notablyWestNile virus and, by some evidence, severe forms of influenza.
3. Off-target editing. Subsequent analysis of the experimental data showed signs of mosaicism — one of the twins apparently had cells with both edited and uneditedCCR5.The outcome was not whatHe had intended.
4. Absence of informed consent. The parents were not fully informed of the risks or the available alternatives.This violated the foundational standards of biomedical ethics.

Part 3.Where theEthicalBoundaryLies

Bioethics offers several key principles for distinguishing acceptable from unacceptable genomic intervention:

• The therapy vs. enhancement distinction: correcting a mutation causing severe disease is therapy.Modifying genes affecting intelligence or appearance in a healthy child is enhancement.Most bioethicists and regulators draw the boundary here — though in practice it blurs: what counts as disease, and what as a variant of normal?
• The heritability principle: germline modifications are passed to all descendants and cannot be recalled.This qualitatively distinguishes embryo editing from any other medical intervention.This is why most expert consensus statements require a significantly higher standard of evidence and public deliberation than for somatic gene therapy.
• The autonomy of the future person: a child whose genome is edited before birth has not given consent.To what extent do parents have the right to make irreversible decisions about their child's biology?

Part 4.WhatComesNext:Technologies on theHorizon

Several directions that are in active research as of 2025 and may transform reproductive medicine within the next decade:

• In vitro gametogenesis (IVG): producing eggs and sperm from ordinary somatic cells (for example, skin cells) via induced pluripotent stem cells (iPSCs).In 2023,Japanese researchers produced live mouse pups from eggs grown this way.In humans — years of work and significant ethical barriers remain.
• In utero gene therapy: treating genetic conditions in the foetus before birth.In 2024, the first clinical trials of in utero therapy for spinal muscular atrophy showed promising results.The critical distinction from germline editing: only the individual child is treated, and the changes are not inherited.
• Expanded newborn screening based onWGS: whole-genome sequencing of newborns.Pilot programmes are already running in theUK (theGenomicsEngland project) and severalUS states.The goal is to identify hundreds of rare genetic conditions before symptoms appear, while the therapeutic window is still open.

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