discuss the social and ethical considerations of using genetic screening and gene therapy in medicine

Genetic Technology Applied to Medicine and Beyond

Learning objective

Discuss the social, ethical, legal and scientific considerations of genetic screening, gene therapy and other biotechnological applications, linking them to the core techniques of the Cambridge International AS & A Level Biology syllabus (Topic 19 – Genetic Technology) and to relevant regulatory frameworks.

1. Core biotechnological techniques

1.1 Recombinant DNA & cloning

• Restriction enzymes cut DNA at specific sequences (e.g., EcoRI at 5’‑GAATTC‑3’).
• DNA ligase joins compatible ends, creating a recombinant plasmid.
• Vectors – plasmids, bacteriophages, viral genomes – carry the gene of interest.
• Cloning steps: (i) isolate gene, (ii) insert into vector, (iii) transform host cells, (iv) select transformants (antibiotic resistance, blue/white screening), (v) confirm by colony PCR or sequencing.

1.2 Polymerase Chain Reaction (PCR) & DNA sequencing

• PCR amplifies a specific DNA fragment using primers, a thermostable DNA polymerase (Taq), and thermal cycling.
• Quantitative PCR (qPCR) provides real‑time measurement of DNA quantity – essential for viral load monitoring and copy‑number analysis.
• Sanger sequencing (chain‑termination) and next‑generation sequencing (NGS) give base‑level information for mutation detection, carrier testing and whole‑genome screening.

1.3 Gene‑editing technologies

1.4 Detecting off‑target activity

• GUIDE‑seq – integrates a double‑stranded oligodeoxynucleotide at cleavage sites, sequenced to map off‑targets.
• Digenome‑seq – whole‑genome sequencing of in‑vitro digested DNA.
• Site‑specific PCR & deep‑sequencing – quantifies indel frequency at predicted off‑target loci.

2. Production of transgenic organisms

2.1 Plants

• Bt cotton & maize – Agrobacterium‑mediated insertion of Bacillus thuringiensis toxin gene confers insect resistance.
• Golden Rice – β‑carotene biosynthesis genes from daffodil and bacteria introduced to combat vitamin A deficiency.

2.2 Animals

• GloFish – Zebrafish engineered with fluorescent protein genes for ornamental trade.
• Insulin‑producing goats – Mammary‑gland‑specific expression of human insulin gene; milk harvested for pharmaceutical use.

2.3 Microbes

• Recombinant E. coli (Humulin) – Plasmid‑borne human insulin gene expressed, purified for diabetes treatment.
• Engineered yeast (bio‑ethanol, artemisinin) – Metabolic pathway optimisation for industrial production.

3. Applications of genetic technology

3.1 Diagnostics & genetic screening

• Pre‑conception carrier testing – Detects recessive alleles (e.g., CFTR for cystic fibrosis).
• Newborn screening – Heel‑prick blood spots analysed by tandem mass spectrometry for PKU, galactosaemia, SCID.
• Predictive testing for adult‑onset disorders – BRCA1/2, Huntington’s disease, Lynch syndrome.
• Pharmacogenomics – CYP2C19 for clopidogrel, TPMT for thiopurines, HLA‑B*57:01 for abacavir hypersensitivity.

Quantitative example (PKU newborn screening)

The relatively low PPV illustrates why confirmatory diagnostic testing and genetic counselling are essential after a positive screen.

3.2 Therapeutics – gene therapy

• Somatic vs. germ‑line – Somatic edits affect only the treated individual; germ‑line edits are inheritable and currently prohibited for clinical use in most jurisdictions.
• Delivery strategies

  • In‑vivo – Direct injection of viral or non‑viral vectors (e.g., AAV‑mediated retinal therapy).
  • Ex‑vivo – Cells harvested, edited, and re‑infused (CAR‑T cells, hematopoietic stem‑cell therapy).

• Vector comparison

3.3 Agriculture, industry and bio‑security

• GM crops – Herbicide tolerance (e.g., glyphosate‑resistant soy), enhanced nutrition (Golden Rice).
• Biopharmaceuticals – Recombinant vaccines (HBV surface antigen in yeast), clotting factors, monoclonal antibodies.
• Bio‑security – Engineered microbes for bioremediation; dual‑use concerns require containment and monitoring.

4. Ethical, legal and social implications (ELSI)

5. Regulation and policy

• United Kingdom – Human Fertilisation and Embryology Authority (HFEA) for embryo and germ‑line work; Medicines and Healthcare products Regulatory Agency (MHRA) for clinical trials and ATMPs.
• European Union – European Medicines Agency (EMA) issues ATMP guidelines; EU Clinical Trials Regulation (EU‑CTR) standardises trial approval; GMO Directive governs transgenic plants.
• United States – Food and Drug Administration (FDA) classifies gene‑therapy products as biologics; IND applications required; NIH Recombinant DNA Advisory Committee (RAC) reviews research proposals.
• International – World Health Organization (WHO) “Human Genome Editing” recommendations (2021); Cartagena Protocol on Biosafety (UNESCO) for transboundary movement of GMOs.

6. Public engagement and genetic counselling

• School‑based biotechnology modules, media briefings, and community forums to improve scientific literacy.
• Genetic counsellors use decision‑aid tools (risk charts, interactive apps) and adopt a non‑directive approach.
• Patient representatives on research ethics committees ensure that societal values shape policy.

7. Illustrative case studies

7.1 Newborn screening for sickle‑cell disease (SCD)

• Benefit – Early penicillin prophylaxis, vaccination and parental education reduce mortality by > 90 %.
• Ethical/social issues

  • Potential stigma for carriers and families.
  • Decision whether to disclose carrier status to parents of an asymptomatic child.
  • Resource allocation: balancing large‑scale screening costs with lifelong treatment provision.

7.2 In‑vivo CRISPR therapy for Leber congenital amaurosis (LCA10)

• Approach – Single sub‑retinal injection of AAV5‑CRISPR‑Cas9 (EDIT‑101) to correct the CEP290 intronic mutation.
• Regulatory scrutiny – FDA granted “Regenerative Medicine Advanced Therapy” (RMAT) designation; extensive off‑target analysis by GUIDE‑seq before trial launch.
• Debate – Non‑heritable, eye‑specific editing is viewed as low‑risk, yet concerns remain about long‑term safety, cost (£150 k per eye) and equitable access.

7.3 Bt cotton – agricultural biotechnology

• Introduces a bacterial toxin gene conferring resistance to bollworm.
• Economic impact: increased yields and reduced pesticide use in many countries.
• ELSI considerations: gene flow to wild relatives, farmer dependency on patented seeds, and intellectual‑property disputes.

7.4 Recombinant insulin production in E. coli

• Human insulin gene cloned into a plasmid, expressed in bacterial fermenters, purified for therapeutic use.
• Illustrates the link between recombinant DNA, cloning, and a life‑saving medical product.
• Ethical note – ensures a reliable, low‑cost supply compared with animal‑derived insulin, improving global equity.

8. Links to other syllabus topics

• DNA structure & replication – Basis for PCR, sequencing and cloning.
• Inheritance patterns – Carrier testing relies on Mendelian ratios; linkage analysis can locate disease genes.
• Mutation – Understanding point mutations, insertions/deletions, and chromosomal rearrangements underpins gene‑editing strategies.
• Biotechnology regulation – Same agencies that assess GM crops also evaluate gene‑therapy ATMPs, highlighting the common regulatory framework.

9. Suggested diagram

10. Summary

Genetic technology—from recombinant DNA and PCR to CRISPR‑based genome editing—provides powerful tools for diagnostics, therapeutics, agriculture and industry. Successful application requires:

1. A solid grasp of the underlying molecular techniques and their quantitative limits.
2. Robust ethical frameworks that address consent, privacy, discrimination, enhancement, germ‑line modification and ecological impact.
3. Clear, enforceable regulation at national and international levels.
4. Transparent public engagement and high‑quality genetic counselling to align scientific progress with societal values.

When these elements are integrated, genetic technologies can fulfil their promise of personalised, equitable and safe advances in medicine and beyond.