Genetic technology applied to medicine

1. Overview

Genetic technology has three major medical uses. First, genes for useful human proteins can be inserted into host cells so that those cells make recombinant proteins as medicines, giving products that are safer and more reliable than older animal-derived ones. Second, genetic screening reads a person's DNA to detect disease-linked alleles before or after symptoms appear, guiding decisions about treatment, monitoring and reproduction. Third, gene therapy aims to treat the underlying genetic fault by adding a working gene to a patient's cells. Each application raises social and ethical questions about cost, consent, privacy and how far we should alter the human genome.

Key Definitions

• Recombinant protein: a protein made by a host cell (such as a bacterium or yeast) that has been given a gene from another species, usually a human gene.
• Genetic screening: testing an individual's DNA to find out whether they carry a particular allele linked to a genetic disease.
• Gene therapy: treating a genetic disease by inserting a working copy of a gene, or correcting a faulty gene, in a patient's cells.
• Somatic cell gene therapy: gene therapy carried out on body (non-reproductive) cells, so the change is not passed to offspring.
• Germ line gene therapy: gene therapy carried out on gametes or early embryos, so the change would be inherited by future generations.
• Vector: a carrier, often a modified virus, used to deliver a gene into a patient's cells.
• SCID: severe combined immunodeficiency, an inherited disease in which the immune system fails because a key enzyme or receptor is missing.
• Genetic counselling: advice given to individuals or families about the chance of inheriting or passing on a genetic condition, and the options available.

Content

Recombinant human proteins

A human gene can be transferred into a host cell — commonly the bacterium Escherichia coli or a yeast. The host then transcribes and translates the gene and makes a recombinant human protein.

The gene is usually supplied as cDNA (complementary DNA). To make it, mRNA for the protein is extracted from human cells. This mRNA acts as a template, and the enzyme reverse transcriptase builds a complementary DNA copy from it. Because it is copied from mRNA, the cDNA has no introns.

The advantages of producing proteins this way rather than extracting them from animals or human donors are:

• the protein is an exact match to the human version, so it works correctly and is far less likely to cause an immune (allergic) reaction;
• it avoids the risk of transmitting pathogens present in animal or pooled human material;
• it can be made in large, consistent quantities on demand, removing dependence on limited donor supplies;
• it is acceptable to people whose religious or ethical beliefs prevent the use of animal-derived products.

Three examples illustrate the benefits:

• Insulin for type 1 diabetes. Recombinant human insulin replaced insulin extracted from the pancreases of pigs and cattle. Animal insulin differs slightly in amino acid sequence, can cause allergic responses and is limited in supply; the recombinant human protein is identical to the patient's own insulin and can be produced in bulk.
• Factor VIII for haemophilia A, a clotting-factor deficiency. Factor VIII used to be purified from pooled donated blood, which carried a real risk of transmitting blood-borne viruses. The recombinant protein removes this infection risk.
• Adenosine deaminase (ADA) to treat one form of SCID. The recombinant enzyme can be given to replace the missing enzyme, restoring breakdown of toxic metabolites that would otherwise destroy white blood cells. Note that this is enzyme-replacement therapy — giving the patient the protein itself — and is not the same as gene therapy, which is described later.

The table below summarises why the recombinant version is preferred in each case:

Protein	Disease treated	Why the recombinant protein is better
Insulin	Type 1 diabetes	Identical to human insulin (animal insulin differs slightly); no allergic response; unlimited supply
Factor VIII	Haemophilia A	No risk of blood-borne viruses from pooled donor blood; reliable, large supply
Adenosine deaminase (ADA)	One form of SCID	Replaces the missing enzyme so toxic metabolites are broken down; pure, consistent product

Genetic screening

Genetic screening tests a sample of a person's DNA for specific disease-linked alleles. It allows earlier diagnosis, supports informed reproductive choices, and means high-risk individuals can be monitored or take preventive action before symptoms develop. Screening is informed by genetic counselling, which explains the meaning of results and the available options. Examples:

• Breast cancer (BRCA1 and BRCA2). Certain mutated alleles of these genes greatly raise the lifetime risk of breast and ovarian cancer. Note that a positive result here is a raised probability, not a certainty — such a person may never develop cancer, unlike a positive Huntington's result (below), where the dominant allele means the disease will eventually appear. A person who tests positive can choose more frequent screening (so any cancer is found early) or preventive surgery, improving the chance of survival.
• Huntington's disease. This is caused by a dominant allele in which the triplet CAG is repeated too many times; the more repeats, the earlier symptoms tend to begin. Because the allele is dominant, anyone who inherits one copy will eventually develop the disease. Screening lets an at-risk adult know their status and make decisions about having children, since each child of an affected parent has a 50% chance of inheriting the allele.
• Cystic fibrosis. This is caused by a recessive allele of the CFTR gene. Screening identifies symptom-free carriers; if two carriers are planning a family, each child has a one-in-four chance of being affected, so they can seek counselling and consider their options.

Gene therapy

Gene therapy treats a genetic disease at its source by supplying cells with a functioning gene (or correcting the faulty one). A working allele is packaged into a vector — often a modified, harmless virus — which delivers it into the patient's cells, where it is expressed to make the missing functional protein.

• In somatic cell gene therapy the gene is added to body cells only, so the correction treats the patient but is not inherited by their children. Its main limitation is that it may need repeating as treated cells are replaced.
• In germ line gene therapy the gene is added to gametes or an early embryo, so the change would pass to future generations. This is currently not permitted in humans and raises the strongest ethical objections.

Examples:

• SCID. In ADA-deficient SCID, a patient's own bone-marrow stem cells are removed, a working copy of the ADA gene is inserted using a viral vector, and the cells are returned. The corrected cells produce functional white blood cells, restoring immune function. This adds a working gene, so it differs from simply injecting the ADA enzyme.
• Inherited eye diseases. In some inherited forms of blindness caused by a faulty gene in the retina, a working copy of the gene is injected into the eye using a viral vector. The eye is a good target because it is small, easily reached and partly isolated from the immune system, reducing the chance of an immune response against the vector.

Social and ethical considerations

Genetic technology in medicine brings real benefits but also raises issues that students should be able to discuss by giving balanced points on both sides.

Arguments in favour include: it can cure or reduce suffering from previously untreatable diseases; screening allows informed reproductive and lifestyle choices; and treating disease early can reduce long-term healthcare costs.

Concerns against include:

• Privacy and discrimination — genetic data could be misused by employers or insurers, or shared without consent.
• Psychological impact — learning you carry an allele for an untreatable disease such as Huntington's can cause great distress, and the result also reveals information about relatives.
• Consent — testing children or embryos raises questions about who decides.
• Safety and equity — vectors can trigger immune reactions or disrupt other genes; treatments are very expensive, so access may be unequal.
• Germ line and "designer" worries — altering inherited DNA could affect future generations who cannot consent, and could lead to selection for non-medical traits.

Worked example

Exam-style question: Recombinant Factor VIII is now used to treat haemophilia A instead of Factor VIII purified from donated blood. Suggest two advantages of using the recombinant protein. [3]

Model answer:

• It removes the risk of transmitting blood-borne pathogens (such as viruses) that could be present in pooled donated blood.
• It can be produced in large, consistent amounts on demand, so supply does not depend on the number of blood donors.
• The protein is identical to human Factor VIII, so it functions correctly and is less likely to cause an adverse immune reaction.

Worked example

Exam-style question: Cystic fibrosis is caused by a recessive allele (f) of the CFTR gene. A man and a woman are both unaffected carriers. Using a genetic diagram, determine the probability that their child will be (i) affected by cystic fibrosis and (ii) an unaffected carrier. [4]

Model answer:

• Both parents are carriers, so their genotypes are Ff × Ff (F = normal, dominant; f = cystic fibrosis, recessive).
• Each parent produces two types of gamete in equal proportions: F and f.
• Combining the gametes gives the offspring ratio 1 FF : 2 Ff : 1 ff.
• (i) Only the ff genotype is affected, so the probability of an affected child is $\frac{1}{4}$ (25%).
• (ii) Carriers are Ff, which make up 2 of the 4 outcomes, so the probability of an unaffected carrier is $\frac{2}{4} = \frac{1}{2}$ (50%).

Key Equations

This topic is qualitative; there are no equations to learn. The only numerical idea is inheritance probability. For two carriers of a recessive condition (a $\text{Ff} \times \text{Ff}$ cross), the chance a child is affected is: $$P(\text{affected}) = \frac{1}{4} = 25\%$$ For a dominant condition such as Huntington's, each child of one affected (heterozygous) parent has a $\frac{1}{2}$ (50%) chance of inheriting the allele.

Common Mistakes to Avoid

• Saying mRNA is "converted into" cDNA. State that the mRNA acts as a template and the enzyme reverse transcriptase synthesises a complementary cDNA copy from it.
• Describing gene therapy as "changing the gene in every cell" or saying it edits genes in general terms for Huntington's. Be specific: for Huntington's the dominant allele has too many CAG triplet repeats, and gene editing aims to remove the extra repeats; for SCID a working ADA gene is added to the patient's cells.
• Confusing somatic and germ line therapy. Somatic therapy treats body cells and is not inherited; germ line therapy alters gametes or embryos and would be passed to offspring.
• Stating that mutations change the order of amino acids in a gene. Mutations change the nucleotide (base) sequence of DNA; this may then change the order of amino acids in the resulting polypeptide.
• Assuming different cell types contain different genes. Every somatic cell holds the full set of genes; only which genes are expressed differs between cell types.
• Mixing up screening and therapy. Genetic screening only detects a disease-linked allele (diagnosis); gene therapy is a treatment that adds or corrects a gene. Detecting an allele does not change or cure it.
• Calling recombinant ADA "gene therapy". Giving the patient the recombinant ADA enzyme is enzyme-replacement therapy — it supplies the missing protein directly. Only inserting a working ADA gene into the patient's cells counts as gene therapy.
• Giving only one-sided answers to "discuss" questions. Always provide balanced points — advantages and concerns — and finish with a brief judgement if asked.
• Vague benefit statements such as "it's better". Name the specific advantage: identical to the human protein, no pathogen risk, large reliable supply, or avoids animal-derived material.

Exam Tips

• For "explain the advantages" questions, link each example to a named benefit (insulin = identical human protein and bulk supply; Factor VIII = no infection risk; ADA = replaces the missing enzyme).
• In screening answers, state why the result is useful — earlier treatment, monitoring, preventive surgery, or informed reproductive choices — not just that a person "knows they have it".
• Quote whether an allele is dominant (Huntington's) or recessive (cystic fibrosis), and use the correct inheritance probability where relevant.
• For gene therapy, always name the vector (usually a modified virus) and say the gene is expressed to make the functional protein.
• In "discuss" or ethics questions, give at least one point on each side and use precise terms such as consent, privacy, discrimination and germ line.
• Use exact vocabulary throughout: recombinant, vector, somatic, germ line, carrier and template.