The shape of the lesson
By the end of the lesson, learners can
- Gene editing: changes at a chosen site: Pick deletion, insertion or replacement, then press Edit.
- Recombinant human proteins: Choose insulin, factor VIII and ADA in turn.
- Genetic screening and gene therapy: In the medicine tab above, the genetic screening chip shows a test strip for BRCA1, BRCA2, HTT (the Huntington's gene) and CFTR (the cystic fibrosis gene).
- Weighing the ethics: Use the ethics chip in the medicine tab to see benefits and concerns balanced on a scale.
- Recombinant proteins: insulin, factor VIII, ADA: identical to human, safe, plentiful.
- Screening: BRCA1/2, Huntington's, cystic fibrosis: informed choices, early action.
- Gene therapy: SCID (stem cells + viral vector), eye (AAV under the retina); somatic only.
- Ethics: consent, privacy, discrimination, cost, safety, embryos, germ line.
One picture every idea returns to
Gene editing is a form of genetic engineering in which DNA is inserted, deleted or replaced at a specific site in the genome, for example using a guide RNA to lead a nuclease to the target. Recombinant human proteins such as insulin (diabetes), factor VIII (haemophilia) and adenosine deaminase (one form of SCID) are identical to the human proteins, made in large amounts and free from the infection risks of animal or donor sources. Genetic screening tests DNA for particular alleles, such as harmful BRCA1 and BRCA2 alleles (breast cancer), the Huntington's disease allele and cystic fibrosis alleles, so people can make informed decisions and start treatment early. Gene therapy adds a working allele to a patient's cells using a vector, as in treatments for SCID and inherited eye diseases. All of these raise social and ethical questions about consent, privacy, discrimination, cost, safety and the limits of what should be changed.
Forty-five minutes, phase by phase
| Time | Phase | What happens in the room | Grouping |
|---|---|---|---|
| 0 to 5 min | Hook: predict | Open with the question in the title, Making medicines, reading risks, repairing genes.. Genetic technology now makes human proteins in bacteria and cultured cells, tests people for disease alleles before symptoms appear, and inserts working alleles into a patient's cells. Put the figure on the board: it is the one picture every idea in the lesson returns to. | Whole class, then pairs |
| 5 to 11 min | Teach and check: Gene editing: changes at a chosen site | Pick deletion, insertion or replacement, then press Edit. Project tab 6 of the lab (Genetic technology lab, gene editing) and let a student drive it while the class predicts. | Whole class, then pairs |
| 11 to 17 min | Teach and check: Recombinant human proteins | Choose insulin, factor VIII and ADA in turn. Project tab 7 of the lab (Genetic technology lab, medicine) and let a student drive it while the class predicts. | Pairs |
| 17 to 23 min | Teach and check: Genetic screening and gene therapy | In the medicine tab above, the genetic screening chip shows a test strip for BRCA1, BRCA2, HTT (the Huntington's gene) and CFTR (the cystic fibrosis gene). | Pairs |
| 23 to 30 min | Teach and check: Weighing the ethics | Use the ethics chip in the medicine tab to see benefits and concerns balanced on a scale. | Jigsaw |
| 30 to 36 min | Check | The four Stage 1 questions from the student lesson, answered on mini whiteboards or by show of fingers. Re-teach the one most get wrong. | Individual, then whole class |
| 36 to 43 min | Plenary | The exam-style questions from Stage 2, one at a time: thirty seconds alone, then a random call. The feedback lines in the key give the examiner's wording. | Individual, random call |
| 43 to 45 min | Exit and homework | Set the worksheet below (6 questions, 18 marks). Learners self-assess against the objectives before they leave. | Individual |
Protect the parts that carry the learning
The sequence carries about fifty minutes of material, so the lab is driven by one student while the class predicts rather than explored freely. Times are a guide.
Protected: the check at 30 minutes. It is the only individual read on whether the key idea landed, and it is not cut.
Cut first if the build overruns: the last check in Weighing the ethics, never the check or the plenary.
In a 60 minute block: run worksheet questions 1 to 3 in class as a Rally Coach set and model both the hardest worked example and its check live.
Jigsaw
Split the content into expert pieces. Expert groups master one piece each, then regroup so every home team has one expert per piece, and each expert teaches their piece to the team.
The full structure, with its variations and the other twelve, is on the cooperative-learning page.
What to head off, and how
| Trap learners fall into | Teaching move that pre-empts it |
|---|---|
| Bacteria cannot add sugar groups or modify proteins the way human cells do, so some recombinant human proteins, such as factor VIII, are made in cultured mammalian cells instead. | Return to Recombinant human proteins: ask a pair to state the correct version and show it on the lab before moving on. |
Genetic technology in medicine: worksheet
6 questions, 18 marks. Written in the style of the papers; no past paper question is reproduced.
Explain the advantages of treating haemophilia with recombinant factor VIII rather than factor VIII purified from donated blood.
Explain what is meant by gene editing and name the three types of change it can make.
Outline how gene therapy has been used to treat severe combined immunodeficiency (SCID) caused by a lack of adenosine deaminase.
Outline the advantages of genetic screening for harmful alleles of BRCA1 and BRCA2.
Suggest why inherited eye diseases were among the first conditions to be treated successfully by gene therapy.
Discuss the social and ethical considerations of offering genetic screening for Huntington's disease to adults with an affected parent.
Answer key and marking notes
- No risk of transmitting infections such as HIV or hepatitis that can be present in donated blood.
- Supply is reliable and can be produced in large quantities, not limited by the number of blood donors.
- It is human factor VIII, so it is less likely to provoke an immune response; made in mammalian cells, it has the correct sugar groups.
- Gene editing is a form of genetic engineering in which DNA is changed at a specific, targeted site in the genome.
- It can insert, delete or replace DNA (bases) at that site.
- Bone marrow stem cells are removed from the patient.
- A normal allele of the ADA gene is inserted into the cells using a vector, such as a modified (harmless) virus.
- The modified cells are grown and returned to the patient (after treatment to make room in the bone marrow).
- They divide and produce lymphocytes that make ADA, so the immune system works; this is somatic therapy, not passed on to offspring.
- Carriers of harmful alleles have a much higher risk of breast (and ovarian) cancer, so they can be identified before cancer develops.
- They can have more frequent checks (mammograms / MRI), so any cancer is found early when treatment is more successful.
- They can choose preventive surgery or medication; relatives can also be tested.
- The eye is small and easy to reach, so the vector can be injected directly under the retina into the target cells, and only a small dose is needed.
- The eye is partly protected from the immune system, so the vector is less likely to be destroyed or cause inflammation (and effects can be checked by testing vision).
- For: a negative result removes uncertainty; a positive result allows planning of future care, careers and finances.
- For: informed decisions about having children (for example embryo testing).
- Against: there is no cure, so a positive result may cause severe anxiety or depression; some people prefer not to know.
- Against: results affect relatives who may not want to know; possible discrimination by insurers or employers and concerns about privacy; counselling is needed before and after testing.
8 multiple-choice questions on this lesson
From the topic question bank. Assign them in the app for a marked score in your gradebook, or run the topic as a class game.
In gene editing, what determines the exact site in the genome where the nuclease cuts the DNA?
- Aa guide RNA whose base sequence is complementary to the target DNA
- Ba promoter inserted next to the target gene
- Ca fluorescent marker gene placed beside the target
- Da primer that binds to the target at about 55 °C
People with haemophilia were once treated with factor VIII purified from donated blood. What is the main advantage of recombinant factor VIII?
- Athere is no risk of passing on infections such as HIV or hepatitis from blood donors
- Ba single dose permanently cures haemophilia
- Cit can be taken as a tablet instead of by injection
- Dit is made cheaply by bacteria in large fermenters
Why are GM bacteria suitable for producing large amounts of human insulin?
- Athey reproduce rapidly and can be grown in large fermenters, so a lot of insulin is made at low cost
- Bthey can add sugar groups to proteins in the same way as human cells
- Cthey naturally contain the human insulin gene, which only needs switching on
- Dthey can remove the introns from human genes before translation
Huntington's disease is caused by a dominant allele. A woman's father has Huntington's disease and is heterozygous; her mother does not have the allele. Before any genetic test, what is the probability that the woman inherited the Huntington's allele?
- A50 %
- B25 %
- C75 %
- D100 %
Carriers of a cystic fibrosis allele have no symptoms. Why is screening for carriers still useful?
- Aif both partners are carriers, each child has a 1 in 4 chance of cystic fibrosis, so they can make informed choices
- Bcarriers will develop cystic fibrosis later in life, so they can begin treatment early
- Ccarriers can only pass the allele to sons, so they can choose to have daughters
- Dcarriers can have the allele removed from all their cells by gene therapy before they have children
The pedigree shows a family affected by cystic fibrosis, which is caused by a recessive allele. Individual 4 does not have cystic fibrosis. What is the probability that individual 4 is a carrier?
- A2/3
- B1/2
- C1/4
- D3/4
In gene therapy for inherited blindness caused by a faulty RPE65 gene, a harmless virus carrying the normal gene is injected directly under the retina rather than into the bloodstream. Which is the best reason?
- Athe vector reaches the retinal cells that need the gene in a high dose, and the eye is partly shielded from the immune system
- Bretinal cells are the only cells in the body that can take up viruses
- Cthe RPE65 gene is expressed in red blood cells, so blood would destroy it
- Dinjecting into the blood would make the change pass on to the patient's children
Somatic gene therapy is used in medicine, but germ-line gene therapy, which alters eggs, sperm or early embryos, is not permitted in humans in most countries. Which is the main reason?
- Agerm-line changes would be inherited by future generations who cannot consent, and long-term effects are unknown
- Bgerm-line cells are unable to take up DNA from any vector
- Csomatic therapy changes the DNA of every cell in the body, so it is more effective
- Dgerm-line therapy can only be carried out in bacteria, not in humans
Quiz key
A guide RNA pairs with the target by complementary base pairing and brings the nuclease to that site, so changing the guide sequence changes the target. Promoters control transcription, not cutting. Marker genes show expression after a transfer. Primers mark the region copied in PCR; they do not direct a nuclease.
Recombinant factor VIII contains no human blood products, so it cannot carry blood-borne viruses, and its supply does not depend on donors. It replaces the missing protein but does not change the patient's genes, so regular treatment is still needed. It is a protein and would be digested if swallowed. It is made in cultured mammalian cells, not bacteria, because the protein needs sugar groups added.
Bacteria divide quickly and can be grown in huge numbers in fermenters, giving a reliable, cheap supply. They cannot add sugar groups like human cells, which is why some proteins are made in mammalian cells; insulin does not need them. The human gene must be inserted; bacteria do not have it. Bacteria cannot splice out introns, which is why cDNA is used.
The father (Hh) passes H in half of his gametes and the mother (hh) always passes h, so each child has a 1 in 2 (50 %) chance of being Hh. 25 % is the chance of an affected child from two carriers of a recessive allele. 75 % applies to a cross between two heterozygotes for a dominant allele. 100 % would need the father to be homozygous HH.
Two heterozygous carriers have a 1 in 4 chance of an affected (homozygous recessive) child with each pregnancy, so knowing allows them to consider options such as embryo testing. Carriers are heterozygous and do not develop the disease. The CFTR gene is on an autosome, so sons and daughters inherit it equally. Gene therapy treats some body cells; it cannot remove an allele from every cell or from the gametes.
Individual 3 has cystic fibrosis (ff), so both unaffected parents must be carriers (Ff). Their children are FF : Ff : ff in the ratio 1 : 2 : 1. Individual 4 is unaffected, so ff is excluded, leaving FF : Ff = 1 : 2, a probability of 2/3. 1/2 is the chance of a carrier among all children of two carriers. 1/4 is the chance of an affected child. 3/4 is the chance of an unaffected child, not of a carrier.
Injecting under the retina delivers the vector straight to the cells that need RPE65, so a small dose is effective, and the eye's partial protection from the immune system reduces the chance of the vector being attacked. Many cell types can be infected by viruses, which is why delivery matters. RPE65 is needed in the retina, not in red blood cells. Somatic therapy by either route does not alter the gametes.
A germ-line change would be copied into every cell of the resulting person and passed to their descendants, none of whom can consent, and unforeseen harmful effects could spread through a family; this also raises fears of 'designer babies'. Germ-line cells can be modified technically, which is why it is regulated. Somatic therapy changes only the treated cells, not every cell. Germ-line modification is technically possible in mammals, so it is not limited to bacteria.
What to project
The student lesson embeds these tabs. Open them full screen on the projector; every slider has a drag handle on the stage.
Slides for this lesson
A projectable deck for every pack is on the way. Until then, present the student lesson full screen: its sections, figure and lab tabs follow the same order as the plan above.