Genetic Prevention: Screening and Engineering

Q1, Marking guidelines, budget allocation (8 marks)

What each option can achieve (2 marks). 1 mark for explaining that Options A and B act on single-gene conditions with a known inheritance pattern: carrier screening identifies couples who both carry the same recessive variant and therefore face a one in four risk in every pregnancy, and PGT-M selects between IVF embryos for a variant already identified in that family. Neither alters DNA. 1 mark for explaining that Option C targets a multifactorial disease, where dozens or hundreds of variants each contribute small risk and environment does much of the rest, so no genetic selection or editing could address it and prevention must act on modifiable exposure instead.

Accounting for the difference in scale (2 marks). 1 mark for identifying that the gap is not a measure of how well each intervention works but of how common the target condition is: cystic fibrosis, SMA and fragile X are individually rare, so even effective prevention avoids tens of cases, whereas Type 2 diabetes affects a large share of the population, so a modest per-person effect applied to five million people yields thousands. 1 mark for connecting this to attributable risk reasoning: the largest removable share of disease burden lies with the common multifactorial condition, which is why cost per case avoided differs by two orders of magnitude.

Equity of access (2 marks). 1 mark for identifying Option B as the least equitable: six metropolitan clinics requiring travel and multiple visits, on top of IVF cost and physical burden, restricts it to families who can pay and travel, so it cannot reduce disease at population level, the standard any public-health measure must meet. 1 mark for contrasting Option A, delivered through GPs statewide and Medicare funded, and Option C, delivered where the population already is, both of which are structurally accessible.

Judgement (2 marks). 1 mark for an explicit, data-referenced allocation. 1 mark for resisting the "cheapest wins" trap. A Band 6 answer allocates the majority of the budget to Option C on attributable-risk grounds while arguing that Options A and B are not competing with it, because they address conditions Option C cannot touch at all: a family facing a one in four recurrence risk for cystic fibrosis gains nothing from a diabetes campaign. It therefore retains Option A, which is cheap relative to B, reaches the whole state and delivers information families can act on with counselling, and either retains Option B at reduced scale with support for travel and accommodation to address the access barrier, or notes explicitly that funding it as configured buys the fewest cases avoided at the highest cost with the worst equity. Accept any defensible allocation that recognises the two categories are not interchangeable.

Band guidance. Band 6 distinguishes monogenic from multifactorial prevention as the organising argument and explains the scale difference as prevalence rather than efficacy. Band 4 ranks the options on cost per case avoided alone, or asserts that genetic technology is "better" without addressing what each can biologically achieve.

Q2, Marking guidelines, source critique (8 marks)

Award 1 mark for each error correctly identified and 1 mark for each accurate correction, to a maximum of 6, plus up to 2 marks for the judgement. Expected errors include:

• "Edit out the faulty gene in any patient and their descendants will be free of it forever." This conflates somatic with germline editing. Casgevy, the approved CRISPR medicine, edits the patient's own blood stem cells outside the body, so the change is somatic and cannot be inherited. The patient's children face exactly the same risk they always did.
• "In any patient." Approved editing and gene therapy target one gene in one accessible tissue, and in Casgevy's case the cells can be removed, edited outside the body where the edit is checked, and returned. Delivery to most organs remains unsolved, the gene must fit the vector, and vector immunity limits repeat dosing.
• "Australian families should be offered embryo editing immediately; only red tape stands in the way." Implanting a genetically modified embryo is an offence in Australia under the Prohibition of Human Cloning for Reproduction Act 2002. The objections are substantive rather than procedural: consent is impossible from a person who does not yet exist, off-target changes would themselves be inherited, and the effects cannot be recalled. The 2018 Chinese case drew international condemnation and a prison sentence.
• "Preimplantation testing merely edits embryos less precisely." PGT does not edit anything. It is selection: embryos are biopsied at the blastocyst stage and those without the known variant are transferred, and no embryo's DNA is altered at any point. It is also not obsolete; it is the established option for a family with a known single-gene variant.
• "Will end all inherited disease." Most of the disease burden is multifactorial, with many variants each contributing small risk plus a large environmental component, so there is no single gene to select against or edit. Broad testing also returns variants of uncertain significance, which create anxiety without an actionable decision.
• "Cost is irrelevant because prices always fall." Cost is central to whether a method prevents disease across a population. Zolgensma costs around 2.5 million dollars per dose and IVF with PGT costs thousands per cycle, with both concentrated in major cities. A prevention method available only to families who can pay and travel does not reduce population disease and can widen health gaps. Asserting future price falls is not evidence.
• Two technical omissions. The column ignores off-target effects, where the guide RNA binds a similar sequence and Cas9 cuts the wrong gene, and mosaicism, where editing an embryo succeeds in some cells and not others, leaving a patchwork individual.
• Source quality. No author expertise, study citation or funding statement is given, so no claim can be traced or corroborated.

Judgement (2 marks). The realistic current scope is narrow but genuine. Established and effective: newborn and reproductive carrier screening with non-directive counselling, prenatal screening and diagnosis, and PGT-M for families with a known variant. Genuine but narrow: approved somatic therapies for specific single-gene conditions in accessible tissues, which treat patients without preventing inheritance. Not available and prohibited in Australia: germline editing, the only intervention that would make a change heritable. Outside the reach of genetic prevention altogether: the multifactorial conditions that make up most of the disease burden, which remain the territory of prevention campaigns. Full marks require the student to affirm the real capability, Casgevy is a genuine breakthrough, while rejecting the extrapolation from it, and to use cautious wording such as "can reduce risk in specific cases" rather than "prevents genetic disease".