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. Each of these brings benefits, and each raises questions that society has to answer.
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.
Fig. 1: somatic gene therapy for SCID caused by lack of adenosine deaminase; the patient's own stem cells are given a normal allele outside the body and then returned
Section 01
Gene editing: changes at a chosen site.
Pick deletion, insertion or replacement, then press Edit. The nuclease with its guide RNA moves to the highlighted target (six base pairs), cuts both strands, and the cell repairs the cut. In insertion and replacement the new bases appear in green.
What it is: gene editing is genetic engineering in which DNA is inserted, deleted or replaced at a specific, chosen site in the genome. Older methods added genes at random positions.
How the site is found: in systems such as CRISPR-Cas9, a short guide RNA has a base sequence complementary to the target DNA. It binds there by complementary base pairing and leads a nuclease (an enzyme that cuts nucleic acids) to that exact place, where both strands are cut.
Deletion: the cut ends are joined, removing or disrupting a section and so knocking out a gene.
Insertion: a supplied DNA template with ends matching the cut is copied into the gap, adding new bases.
Replacement: a faulty sequence is cut out and a correct version is copied in, for example correcting a disease-causing allele.
Section 02
Recombinant human proteins.
Choose insulin, factor VIII and ADA in turn. Notice that factor VIII is made in cultured GM hamster cells, not bacteria. The other chips (genetic screening, gene therapy: SCID, gene therapy: eye and ethics) go with the next two sections below.
Protein
Treats
Older source
Advantages of the recombinant protein
insulin
type 1 diabetes
pancreases of pigs and cattle
identical to human insulin, so fewer allergic or immune reactions; made in large quantities by GM bacteria or yeast at lower cost; reliable supply; no risk of animal diseases; avoids ethical and religious objections to using animal products
factor VIII
haemophilia A (a blood-clotting protein is missing)
plasma from donated human blood
no risk of infections such as HIV or hepatitis from donated blood; supply does not depend on donors; made in mammalian cells, which add the sugar groups the protein needs
adenosine deaminase (ADA)
ADA deficiency, one cause of severe combined immunodeficiency (SCID)
enzyme from cattle
human enzyme, so less likely to cause an immune response; given by injection to restore some immune function until gene therapy or a bone marrow transplant
Examiner trap
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.
Stage 1 · Learn
Check what the sim just showed you
Four quick checks. Each correct answer earns XP and records this skill on your profile.
Quick check+10 XP
In the gene editing simulator, what leads the nuclease to the highlighted target site?
Quick check+10 XP
You choose replacement and press Edit. What happens at the target?
Quick check+10 XP
The medicine simulator shows factor VIII being made by GM hamster cells in culture. Why are mammalian cells used rather than bacteria?
Quick check+10 XP
In the simulator's SCID gene therapy, which cells receive the normal ADA allele?
Section 03
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). The two gene therapy chips show a viral vector and stem cells for SCID, and an injection under the retina for inherited eye disease.
Genetic screening analyses a person's DNA to find whether they carry particular alleles. It can be done on adults, children, newborns, fetuses or embryos made by IVF (pre-implantation genetic diagnosis).
BRCA1 and BRCA2: these tumour suppressor genes help repair DNA. Some alleles greatly raise the risk of breast and ovarian cancer. A person who knows they carry one can have more frequent screening (mammograms, MRI) or choose preventive surgery.
Huntington's disease: caused by a dominant allele, with symptoms usually starting in middle age. A test shows whether a person will develop the disease, which helps with decisions about having children and planning for the future, but there is no cure.
Cystic fibrosis: caused by recessive alleles of the CFTR gene. Screening finds carriers, so couples can know the chance of having an affected child; embryos and fetuses can be tested; newborns are screened so treatment can start early.
Gene therapy inserts a normal allele into the cells of a person with a genetic disease, using a vector such as a harmless virus or liposomes. In somatic gene therapy only body cells are changed, so the change is not passed to children.
SCID: children have almost no working immune system. Bone marrow stem cells are removed, a normal allele (for example the ADA gene) is inserted with a viral vector, and the cells are returned, where they produce working lymphocytes. In some early trials the virus inserted next to a gene that controls cell division and caused leukaemia; newer vectors are safer.
Inherited eye diseases: in Leber congenital amaurosis a faulty RPE65 gene causes blindness. A harmless virus (AAV) carrying a normal copy is injected under the retina; retinal cells make the missing protein and vision improves. The eye is small, easy to reach and partly shielded from the immune system, so it is a good target.
Section 04
Weighing the ethics.
Use the ethics chip in the medicine tab to see benefits and concerns balanced on a scale. Exam questions ask you to discuss both sides.
Benefits
Concerns
early diagnosis and treatment; informed decisions about health and having children
anxiety and stress, especially for untreatable conditions such as Huntington's disease
preventive action for people at high risk of cancer
who should be told: relatives share alleles, so a result affects the whole family
treatment of previously incurable diseases by gene therapy
privacy, and possible discrimination by employers or insurance companies
fewer children born with severe genetic diseases
selection or termination of embryos and fetuses; where to draw the line between disease and other traits ("designer babies")
knowledge that drives new therapies
high cost and unequal access; long-term safety of gene therapy; germ-line changes would affect future generations without their consent, and are banned in humans in most countries
Stage 2 · Exam
Exam-style questions
Unlocks once the four checks above are done. Worth more XP, written to A Level Paper 4 standard.
Finish the four checks above to unlock the exam questions
Exam style+20 XP
Which is an advantage of using recombinant human insulin rather than insulin extracted from pigs?
Exam style+20 XP
Why does screening for Huntington's disease raise more ethical concern than screening newborns for cystic fibrosis?
Exam style+20 XP
A child is treated for SCID by somatic gene therapy. Which statement is correct?
Exam style+20 XP
Which describes gene editing rather than older methods of genetic engineering?
Skill unlocked
Genetic technology in medicine, mastered.
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