Lesson 8: Cell Division

Your body makes about 2 million new red blood cells every second — cell division on a staggering scale, normally under exquisite control. When control fails, the result is cancer, one of the leading causes of death worldwide. This lesson revisits the cell cycle with its checkpoints, details the regulation of division, explains how mutations in proto-oncogenes and tumour-suppressor genes cause cancer (and how it is treated), and explores stem cells — their potency, therapeutic uses from bone-marrow transplants to regenerative medicine, and the ethical debates they provoke.

The cell cycle and its checkpoints

The cell cycle: G1 (growth, organelle replication), S (DNA replication — each chromosome becomes two sister chromatids), G2 (growth, synthesis of mitotic proteins), then mitosis (prophase, metaphase, anaphase, telophase) and cytokinesis. Checkpoints police the cycle: the G1 checkpoint (is DNA undamaged? is the cell large enough? — the restriction point committing the cell to division), the G2 checkpoint (is DNA fully replicated and undamaged?) and the spindle checkpoint in metaphase (are all chromosomes attached to spindle fibres?). Failed checkpoints trigger repair or apoptosis (programmed cell death).

Cyclins and cyclin-dependent kinases (CDKs) drive the cycle: cyclin levels rise and fall, activating CDKs that phosphorylate target proteins to advance the cycle. This molecular detail earns A-level marks: "cyclins bind CDKs, activating them to trigger the next stage." Growth factors (e.g. platelet-derived growth factor, PDGF) signal cells to divide — linking division to the body's needs, as in wound healing, where division continues until contact inhibition stops it.

The mitotic index (Lesson 2) measures the proportion of cells in mitosis — high in growing tissues (root tips, bone marrow, cancers). Exam questions give cell counts per stage and ask for the mitotic index and its interpretation, or ask why a tissue has a high index (rapid growth/repair) versus a low one (e.g. brain, mostly non-dividing).

Cancer — division out of control

Cancer is uncontrolled mitosis forming tumours. It arises from mutations in two gene classes: proto-oncogenes (which normally promote division, e.g. growth-factor receptors) mutate into oncogenes that drive division constitutively — like a stuck accelerator; tumour-suppressor genes (e.g. p53, "guardian of the genome", which halts the cycle for repair or triggers apoptosis) are inactivated — like cut brakes. Both failures together allow a cell to divide without restraint. Carcinogens (tobacco smoke, UV, asbestos, some viruses like HPV) increase mutation rates.

Benign tumours grow slowly, remain encapsulated, and do not spread; malignant tumours invade surrounding tissues and metastasise — cells break off, travel in blood or lymph, and seed secondary tumours. Malignancy, not the primary tumour, usually kills (by disrupting vital organs). Risk factors: smoking (lung, mouth, throat), UV exposure (melanoma), diet/obesity/alcohol (bowel, breast), infections (HPV → cervical cancer, H. pylori → stomach cancer), age (mutations accumulate) and inherited mutations (BRCA1/2).

Treatments exploit rapid division: surgery (removes localised tumours), radiotherapy (damages DNA in the beam's path — fractionated doses let healthy cells recover), chemotherapy (drugs targeting dividing cells — hence side effects in hair follicles, gut lining and bone marrow), immunotherapy (monoclonal antibodies marking cancer cells; checkpoint inhibitors unleashing T cells) and targeted therapies (e.g. Herceptin for HER2-positive breast cancer). Evaluate: surgery cannot reach metastases; chemo/radiotherapy harm healthy dividing cells; targeted therapies need the right molecular marker; early screening (mammograms, bowel screening) dramatically improves survival — prevention and early detection outweigh treatment advances.

Stem cells — potency and sources

Potency hierarchy: totipotent (zygote — can form a complete organism including placenta), pluripotent (embryonic stem cells — any body cell type), multipotent (adult stem cells — limited lineages, e.g. haematopoietic stem cells → all blood cells), unipotent (e.g. muscle satellite cells → muscle only). Sources: embryos (IVF surplus — pluripotent, ethically contentious), umbilical cord blood (multipotent, banked at birth), adult tissues (bone marrow, gut lining — multipotent, no ethical issues but harder to culture) and induced pluripotent stem cells (iPS — adult cells reprogrammed with transcription factors, pluripotent without embryos).

Therapeutic uses in practice: bone-marrow/haematopoietic transplants for leukaemia and lymphoma (routine for decades); skin grafts grown from stem cells for burns; limbal stem cells restoring corneas; clinical trials for Parkinson's (dopamine neurones), spinal-cord injury (oligodendrocytes), type 1 diabetes (insulin-producing β cells) and heart repair after infarction. Therapeutic cloning (somatic-cell nuclear transfer) could create patient-matched tissues, avoiding rejection — still largely experimental.

Plant meristems are the botanical equivalent — totipotent stem cells enabling micropropagation: thousands of identical, virus-free plants (orchids, bananas, potatoes) from tiny explants. This commercial application is examinable and ethically uncontroversial, making it a useful contrast in "discuss" answers.

Ethics of stem cells and cancer screening

Embryonic stem-cell ethics: arguments for — the embryos used are surplus from IVF and would otherwise be discarded; the medical potential (curing Parkinson's, paralysis, diabetes) outweighs the moral cost; regulated research with consent is responsible. Arguments against — embryos are potential human life with moral status; destroying them instrumentalises human life; adult/iPS alternatives exist, making embryo use unnecessary; a slippery slope to reproductive cloning and "designer babies". A balanced answer presents both sides with specifics, then gives a reasoned personal conclusion — examiners reward evaluation, not fence-sitting without reasoning.

Cancer screening ethics parallel the debate: benefits (early detection saves lives — cervical screening prevents ~70% of cervical cancer deaths), harms (false positives causing anxiety and unnecessary treatment; overdiagnosis of harmless abnormalities; cost). Informed consent requires understanding both. Genetic screening for BRCA mutations raises insurance and family implications — who should know, and who decides?

Exam technique for "discuss" questions: structure as arguments for (with evidence/examples), arguments against (with evidence/examples) and a justified conclusion. Use named examples throughout — "bone-marrow transplants cure leukaemia" beats "stem cells treat disease". The conclusion should weigh the strongest arguments, not merely list them.

Uncontrolled division in context — wound healing and tissue repair

Normal division is tightly regulated: growth factors stimulate it (platelets release PDGF at wounds), contact inhibition stops it (cells cease dividing when touching neighbours), and apoptosis removes damaged cells. Wound healing demonstrates control: clotting, inflammation, proliferation (fibroblasts, new capillaries and epithelial cells divide), then remodelling — division switches off when the tissue is restored. Cancer is this system with the off-switch broken.

Tissue-specific division rates reflect function: gut epithelium and bone marrow divide constantly (high mitotic index, vulnerable to chemotherapy); the liver divides rarely but can regenerate massively after partial removal; neurones and heart muscle essentially never divide after development (hence the severity of brain/heart damage, and the excitement about stem-cell repair). "Explain why" questions link division rate to tissue function and to treatment side effects.

Plant cell division concentrates in meristems (root/shoot tips, cambium) — the required-practical root-tip squash samples exactly this zone. Secondary growth (cambium producing xylem/phloem) thickens stems. Comparing plant and animal division control (meristems vs distributed stem cells; no metastasis in plants because cell walls anchor cells in place) makes a strong synoptic paragraph.

Cancer biology in depth

The p53 story in detail: p53 protein monitors DNA damage at the G1 checkpoint. When damage is detected, p53 halts the cycle (activating p21, which inhibits cyclin–CDK complexes) to allow repair; if damage is irreparable, p53 triggers apoptosis by activating pro-death genes. Over half of human cancers carry p53 mutations — without this guardian, damaged DNA replicates, mutations accumulate, and tumours develop. Li-Fraumeni syndrome (inherited p53 mutation) causes multiple early cancers, proving the gene's central role. "Explain" answers trace: carcinogen → p53 mutation → failed checkpoint → damaged cells divide → tumour.

Oncogenes in action: the Ras proto-oncogene encodes a G-protein relaying growth-factor signals; a single point mutation locks Ras in the "on" position, driving division without external signals — found in ~30% of cancers. HER2 (amplified in some breast cancers) is a growth-factor receptor stuck at high output; Herceptin (trastuzumab), a monoclonal antibody blocking HER2, treats exactly these cancers — targeted therapy matched to the molecular defect. This is personalised medicine: test the tumour's genes, then choose the drug.

Tumour progression needs more than division: angiogenesis (tumours secrete VEGF, growing their own blood supply — anti-VEGF drugs starve them), evasion of apoptosis, limitless replication (telomerase reactivation), tissue invasion (enzymes digesting the surrounding matrix) and metastasis. This "hallmarks of cancer" framework organises these capabilities — examiners credit answers that go beyond "uncontrolled division" to name the additional adaptations.

Immunotherapy's logic: cancer cells display abnormal antigens, but tumours suppress T cells via checkpoint proteins (PD-L1). Checkpoint inhibitors (e.g. pembrolizumab) block this suppression, unleashing the patient's own T cells — producing durable remissions in some melanomas and lung cancers. CAR-T therapy engineers the patient's T cells to recognise cancer antigens. Evaluate: spectacular in some cancers, ineffective in others, expensive, and capable of causing autoimmune side effects. The principle — the immune system (Lesson 9) turned against tumours — is pure synoptic biology.

Worked example — mitotic index and stage durations

A root-tip count gives: interphase 340 cells, prophase 28, metaphase 12, anaphase 8, telophase 12 (total 400). Mitotic index = (28 + 12 + 8 + 12) ÷ 400 × 100 = 15% — a vigorously growing tissue. Now use the proportions as a clock: if the whole cycle lasts 24 hours, metaphase occupies 12 ÷ 400 = 3% of it, i.e. 0.03 × 24 × 60 ≈ 43 minutes. This is why stage-frequency data can estimate stage durations — and why interphase, at 85% of the count, must last ~20 hours of the 24. A pathologist handed the same count from adult skin (where the index would be ~1–2%) would read it as a warning sign: division rates this high outside meristem-like tissues suggest loss of checkpoint control.

Common mistakes

• "Both genes must mutate" stated loosely. Precision: one mutant oncogene (a single allele — gain of function is dominant) can drive division, whereas a tumour suppressor usually needs both alleles inactivated (loss of function is recessive at the cell level). That asymmetry is a favourite discriminator.
• Confusing benign with harmless / malignant with fast. The defining feature of malignancy is invasion and metastasis, not growth rate: some benign tumours are dangerous by position (e.g. in the brain), and some malignant cancers grow slowly.
• Stem-cell potency drift. Embryonic stem cells are pluripotent, not totipotent — they cannot form the placenta or a complete organism. Cord-blood and adult stem cells are multipotent. Misgrading potency is an easy mark to lose.
• Ethics answers without conclusions. A "discuss" answer that lists for/against and stops mid-air caps in the middle band. End by weighing: which argument is strongest, and what would change your mind?
• Checkpoint vagueness. Name the checkpoint and its question: G1 (DNA damaged? cell big enough?), G2 (replication complete and error-free?), spindle (all chromosomes attached?). Unnamed "checkpoints check the cell" earns nothing.

Exam Experience

Q1. Explain why most cancers involve mutations in both a proto-oncogene and a tumour-suppressor gene, referring to the different effects of the mutations. [4 marks] Q2. Evaluate the use of embryonic stem cells in medicine. [6 marks]

Mark scheme — Q1: A proto-oncogene mutation is a gain of function: the oncogene drives division constitutively — one mutant allele is enough (accelerator stuck) [1]. A tumour-suppressor mutation is a loss of function: with one working allele the checkpoint still functions, so both alleles usually must be inactivated (brakes cut) [1]. A cell with only one defect is still restrained by the other system [1]; accumulation of both (plus further hallmarks such as angiogenesis) produces malignant growth [1].

Mark scheme — Q2 (level-marked): Level 3: balanced, specific, concluded. Benefits: pluripotent → any cell type; established cures (bone-marrow/haematopoietic transplants for leukaemia); potential for Parkinson's, diabetes, spinal repair; embryos used are surplus IVF that would be discarded. Concerns: embryo destruction/moral status; tumour risk from uncontrolled division; immune rejection unless matched; iPS cells offer an alternative without embryos. The conclusion must weigh the strongest points (e.g. iPS progress shifting the balance) rather than list — unweighed lists cap at level 2.