// Evidence Grader
Claim grades, A through F
Every major claim in this course gets a transparent grade. Audit what's textbook, what's preliminary, and what's hype.
A
Textbook-established
B
Strongly supported
C
Promising / context-specific
D
Preliminary, contested
E
Popular, weak support
F
Misleading or false
A
A typical human cell hydrolyses ~10^9 ATP molecules per second
Biophysical bookkeeping; well-established.
Module 01 · The Cell as a System
D
Single-cell RNA-seq predicts protein abundance accurately
mRNA-protein correlation is modest (r ≈ 0.4); proteomics still required.
Module 01 · The Cell as a System
F
Genetic background fully explains drug response
Cell state, microbiome, age and prior exposure dominate in many cases.
Module 01 · The Cell as a System
A
The Nernst equation predicts ion equilibrium potentials accurately at 37°C
Foundational physical chemistry, used clinically in EP.
Module 02 · Membrane Biophysics & Transport
C
Lipid rafts are stable, microscopically visible domains
Existence of nanoscale ordered domains is supported; large stable rafts are contested.
Module 02 · Membrane Biophysics & Transport
C
Ivacaftor restores function to most CFTR mutations
Effective for gating mutants (G551D); class-specific. Combination needed for F508del.
Module 02 · Membrane Biophysics & Transport
A
Proteasome inhibitors are first-line in multiple myeloma
Standard of care worldwide.
Module 03 · Protein Structure, Folding & Quality Control
C
AlphaFold structures can be used directly for drug design
Useful for orientation; binding-pocket geometry often needs experimental refinement.
Module 03 · Protein Structure, Folding & Quality Control
E
Heat-shock-protein induction extends human healthspan
Strong in worms/flies; unproven and oversold in humans.
Module 03 · Protein Structure, Folding & Quality Control
A
Mannose-6-phosphate is the canonical lysosomal targeting tag for soluble hydrolases
Established cell biology.
Module 04 · Organelles & the Secretory Pathway
A
Rab GTPases mark organelle identity
>60 Rabs each defining specific compartments.
Module 04 · Organelles & the Secretory Pathway
F
Eliglustat cures Gaucher disease
It reduces substrate accumulation; not curative.
Module 04 · Organelles & the Secretory Pathway
A
Microtubules undergo dynamic instability
Mitchison & Kirschner, foundational.
Module 05 · Cytoskeleton & Cell Motility
B
Paclitaxel resistance often involves β-tubulin isotype switching
Supported but tumour-context-dependent.
Module 05 · Cytoskeleton & Cell Motility
F
Cilia are vestigial in adult humans
Primary cilia are critical signaling hubs (Hedgehog, PDGFR) on most cells.
Module 05 · Cytoskeleton & Cell Motility
B
E-cadherin loss promotes invasive epithelial cancer
Classic in lobular breast cancer and diffuse gastric cancer.
Module 06 · Cell Junctions & the Extracellular Matrix
A
Anti-Dsg3 antibodies cause pemphigus vulgaris
Confirmed by passive transfer in mouse.
Module 06 · Cell Junctions & the Extracellular Matrix
F
Generic anti-MMP drugs improve cancer outcomes
Failed in trials; broad MMP inhibition has been a notable disappointment.
Module 06 · Cell Junctions & the Extracellular Matrix
A
ATP synthase is a rotary molecular machine
Direct visualisation by Yoshida & Walker (Nobel 1997).
Module 07 · Bioenergetics & Mitochondrial Cell Biology
B
Mitochondrial donation prevents transmission of severe mtDNA disease
Approved in UK; case-by-case authorisation; outcomes still being collected.
Module 07 · Bioenergetics & Mitochondrial Cell Biology
D
NMN supplementation extends human healthspan
Strong rodent data; human RCTs are small and mixed.
Module 07 · Bioenergetics & Mitochondrial Cell Biology
A
Ras was 'undruggable' for 40 years
Until KRAS G12C inhibitors (sotorasib, adagrasib).
Module 08 · Signal Transduction
C
Biased agonism produces clinically meaningful safety differences
Theoretical strong; oliceridine modestly so in trials.
Module 08 · Signal Transduction
F
All TKIs work indefinitely
Resistance is the rule; sequencing is the strategy.
Module 08 · Signal Transduction
A
H3K4me3 marks active promoters
Established by genome-wide profiling.
Module 09 · Gene Expression & Chromatin
B
Most non-coding GWAS variants act through gene-regulatory elements
Strongly supported by chromatin/eQTL colocalisation.
Module 09 · Gene Expression & Chromatin
D
Phase separation alone explains transcription-factor function
Important emerging concept; specificity vs generality is debated.
Module 09 · Gene Expression & Chromatin
A
mRNA vaccines work by translation of antigen mRNA in transfected cells
Mechanism confirmed; pseudouridine-modified mRNA in LNPs.
Module 10 · RNA Biology & Translation
A
siRNA therapeutics can silence specific transcripts in liver
GalNAc-conjugated siRNAs (inclisiran, patisiran) are clinically used.
Module 10 · RNA Biology & Translation
D
All circulating cell-free miRNAs are reliable biomarkers
Variable preanalytics; specific contexts work, broad use is overstated.
Module 10 · RNA Biology & Translation
A
CDK4/6 inhibitors require Rb for activity
Rb-null tumours are intrinsically resistant.
Module 11 · Cell Cycle & Checkpoints
A
PARP inhibitors are selectively lethal in BRCA1/2-deficient cells
Synthetic lethality demonstrated and validated clinically.
Module 11 · Cell Cycle & Checkpoints
C
Targeting WEE1 will be broadly effective in p53-deficient cancers
Adavosertib trials mixed; manageable but not transformative so far.
Module 11 · Cell Cycle & Checkpoints
A
Venetoclax + azacitidine improves AML survival in older adults
VIALE-A confirmed; standard of care.
Module 12 · Cell Death Pathways
F
Caspase inhibition improves sepsis survival
Trials negative; redundant death pathways take over.
Module 12 · Cell Death Pathways
C
Ferroptosis induction will be a major oncology modality
Promising preclinical; clinical proof-of-concept pending.
Module 12 · Cell Death Pathways
A
BRCA-deficient cancers are sensitive to PARP inhibitors
Synthetic lethality clinically validated multiple settings.
Module 13 · DNA Damage & Repair
B
All MMR-deficient cancers respond to PD-1 blockade
Strong response rates; not 100% — exhaustion and HLA loss escape.
Module 13 · DNA Damage & Repair
D
POLθ inhibitors will succeed where PARP failed
Promising preclinical; clinical data immature.
Module 13 · DNA Damage & Repair
F
Anti-PD-1 monotherapy cures most cancers
Response in subset of tumours/patients; not curative for most.
Module 14 · Cancer Cell Biology
C
Cancer stem cells form a stable hierarchy
True for some hematologic malignancies; plasticity model dominates in many solid tumours.
Module 14 · Cancer Cell Biology
B
ctDNA-guided MRD detection improves outcomes
Strong evidence in CRC (DYNAMIC); other tumours catching up.
Module 14 · Cancer Cell Biology
B
iPSCs and ESCs are functionally equivalent for most uses
Some residual epigenetic memory; but most assays show strong equivalence.
Module 15 · Stem Cells, Development & Regeneration
B
Casgevy (CRISPR-edited HSC) cures sickle cell disease
Sustained benefit in long-term follow-up; long-term safety still accruing.
Module 15 · Stem Cells, Development & Regeneration
F
IV MSC therapy reverses spinal cord injury
No controlled evidence; many predatory offerings.
Module 15 · Stem Cells, Development & Regeneration
A
Pembrolizumab is approved for MSI-H tumours regardless of organ
First tumour-agnostic FDA approval (2017).
Module 16 · Cellular Immunology Essentials
F
All cancer patients should receive checkpoint blockade
Many tumours unresponsive; risk of severe irAE; needs biomarker selection.
Module 16 · Cellular Immunology Essentials
C
Microbiome composition predicts checkpoint response
Repeatedly observed; faecal microbiota transfer trials show modest signals.
Module 16 · Cellular Immunology Essentials
A
Base editing avoids double-strand breaks
Definitional; uses nickase + deaminase.
Module 17 · Methods: Microscopy, Omics & Genome Editing
C
Single-cell atlases capture all cell types in a tissue
Sampling bias, dissociation bias, rare populations missed.
Module 17 · Methods: Microscopy, Omics & Genome Editing
D
AlphaFold-Multimer reliably predicts all protein-protein interactions
Variable; better for stable complexes, worse for transient and antibody-antigen.
Module 17 · Methods: Microscopy, Omics & Genome Editing
B
Onasemnogene abeparvovec is curative for SMA type 1 if given pre-symptomatically
Strong durable benefit; very long-term follow-up incomplete.
Module 18 · Translational Frontier: Cell & Gene Therapy
D
Senolytic combinations (D + Q) extend human lifespan
Encouraging early-phase data; lifespan claims premature.
Module 18 · Translational Frontier: Cell & Gene Therapy
E
Mitochondrial transplant treats heart failure
Single-centre paediatric ECMO data; not standard of care.
Module 18 · Translational Frontier: Cell & Gene Therapy