WBI15/01 – Article potential questions Biology A Level Tutor
Potential questions for Pearson Edexcel International Advanced Level
for use with Question 8 – Unit 5, June 2026
In unit 5, the last question (question 8) is based on a pre-released scientific article a total of 30
marks.
In this document, you will find potential questions and answers for the Scientific Article for
question 8 for Biology IAL (International Advanced Level) WBI15/01.
This document consists of
o Article Summary (237 words) and a more concise version of 54 words. Summary for
each of the 3 subsections
o Five (5) Key Takeaways for the entire article (these are the things you should know
and understand from this article before the exam).
o Key Take aways for each of the 3 subsections and for each paragraph
o Vocabulary and Definitions of unknown words for each paragraph
o Mind Map for the article
o Paragraph Topics and IAL A Level Chapter Mapping
o Full exam-style test paper based on the entire article
o 409 potential questions each with its answer
➢ The questions are based on the scientific article
➢ 80% of them are linked to the syllabus, thus this document can be used for
revision as well
➢ Includes definitions
The article is available at the end of this booklet.
1
,WBI15/01 – Article potential questions Biology A Level Tutor
Entire Article Summary
Summary of the article (237 words):
Fatigue has become increasingly prevalent, particularly following the COVID-19 pandemic, where
it emerged as a core symptom of both acute infection and long covid. Once dismissed as having
no clear biological basis, fatigue is now understood as the product of an ongoing dialogue
between the body and the brain regarding available cellular energy.
Four key brain regions are central to this process: the insula and anterior cingulate cortex (part
of the interoception network), the prefrontal cortex, and the striatum. Together, these regions
perform a continuous cost-benefit analysis, weighing the energy cost of an action against its
potential reward. When energy is insufficient, motivation declines and fatigue results — not from
laziness, but from a biological resource-management calculation.
Several mechanisms can disrupt normal energy supply and cause chronic fatigue. In conditions
like ME/CFS, cells may switch to less efficient fuel sources or fail to produce adequate energy.
Brainstem dysfunction may impair oxygen delivery to muscles via the autonomic nervous system.
Microscopic blood clots, found in long covid and ME/CFS patients, can obstruct small blood
vessels and reduce oxygen transport. Additionally, chronic inflammation triggers cytokine
release, which suppresses striatal activity and conserves energy for immune function —
prolonging fatigue well beyond the initial illness.
Emerging treatments target these specific mechanisms: anti-inflammatory drugs, oxygen-
enhancing therapies, L-DOPA to boost striatal activity, transcranial magnetic stimulation, and
hyperbaric oxygen therapy. Current management strategies include pacing and cognitive
behavioural therapy, though no universal cure yet exists.
The summary of the summary is (54 words):
Fatigue results from the brain's cost-benefit analysis of available cellular energy, involving four
key brain regions. Chronic fatigue, seen in ME/CFS and long covid, stems from impaired cellular
energy production, disrupted oxygen delivery, or persistent inflammation causing cytokine
release. New treatments targeting these specific mechanisms offer hope, though none yet
provide a complete cure.
2
,WBI15/01 – Article potential questions Biology A Level Tutor
Key Take-Aways for the entire article
Key Take-Aways (You need to know and understand the following before the exam):
1. Fatigue is a Biological Process, Not a Lack of Willpower
The brain actively manages energy through a continuous cost-benefit analysis performed
by four key regions: the insula, anterior cingulate cortex, prefrontal cortex, and striatum.
When cellular energy is insufficient, the brain deliberately reduces motivation to conserve
resources. This means fatigue is not a personal weakness or laziness — it is a sophisticated,
biologically driven survival mechanism that prioritises energy for the most essential bodily
functions.
2. All Fatigue Shares a Common Brain Mechanism Despite Having Different Causes
Whether fatigue is triggered by exercise, illness, stress, long covid, or ME/CFS, it manifests
through the same brain network and produces the same fundamental experience. The
causes vary enormously — ranging from poor oxygen delivery to viral infection to
psychological stress — but the end result in the brain is remarkably consistent. As
VanElzakker's forest fire analogy illustrates, different triggers lead to the same outcome.
3. Chronic Fatigue Involves Specific, Identifiable Physical Failures in the Body
Unlike ordinary tiredness that resolves with rest, chronic fatigue involves measurable
biological disruptions. These include cells switching to less efficient fuel sources, brainstem
dysfunction impairing autonomic oxygen delivery, microscopic blood clots blocking
capillaries, and persistent cytokine-driven inflammation suppressing brain activity in the
striatum. These are real, physical, biological failures — not imagined or psychological
symptoms — and this is increasingly supported by scientific evidence.
4. Inflammation is a Central and Recurring Theme Linking Many Forms of Fatigue
Cytokines released during inflammation — whether from viral infection, long covid,
ME/CFS, or even treatment-resistant depression — directly suppress brain activity and
drive fatigue. The immune system consumes enormous amounts of ATP when activated,
leaving insufficient energy for other bodily functions. Chronic inflammation, where this
immune response never fully resolves, appears to be one of the most important and
common underlying mechanisms connecting many otherwise different fatigue conditions.
5. Treatment Must Be Tailored to the Underlying Cause, and Research is Still Evolving
There is currently no single cure for chronic fatigue. Effective treatment depends on
correctly identifying the specific biological cause in each patient — anti-inflammatory
3
, WBI15/01 – Article potential questions Biology A Level Tutor
drugs only help those whose fatigue is inflammation-driven, L-DOPA targets striatal
underactivity, and hyperbaric oxygen therapy addresses oxygen delivery problems.
Patient stories like Lisa Clock's highlight that strategies effective for healthy individuals,
such as pushing through exhaustion, can be actively harmful in chronic fatigue. Pacing and
CBT remain the most accessible current options while more targeted treatments continue
to be developed and trialled.
More Concise Key Take-Aways
1. Fatigue is not weakness → it is the brain's deliberate biological response to low cellular
energy, managed by four interconnected brain regions performing a continuous cost-
benefit analysis.
2. Regardless of its trigger — illness, exercise, or stress → fatigue always manifests through
the same brain network, producing the same fundamental biological outcome.
3. Chronic fatigue involves real, measurable physical failures → inefficient energy
production, brainstem dysfunction, microscopic blood clots, and persistent inflammation.
4. Cytokines released → during chronic inflammation directly suppress brain activity and
redirect energy to the immune system, linking ME/CFS, long covid, and depression
through a common mechanism.
5. No universal cure exists yet → treatment must target the specific underlying cause, while
pacing and CBT remain the most accessible current management options.
4
Potential questions for Pearson Edexcel International Advanced Level
for use with Question 8 – Unit 5, June 2026
In unit 5, the last question (question 8) is based on a pre-released scientific article a total of 30
marks.
In this document, you will find potential questions and answers for the Scientific Article for
question 8 for Biology IAL (International Advanced Level) WBI15/01.
This document consists of
o Article Summary (237 words) and a more concise version of 54 words. Summary for
each of the 3 subsections
o Five (5) Key Takeaways for the entire article (these are the things you should know
and understand from this article before the exam).
o Key Take aways for each of the 3 subsections and for each paragraph
o Vocabulary and Definitions of unknown words for each paragraph
o Mind Map for the article
o Paragraph Topics and IAL A Level Chapter Mapping
o Full exam-style test paper based on the entire article
o 409 potential questions each with its answer
➢ The questions are based on the scientific article
➢ 80% of them are linked to the syllabus, thus this document can be used for
revision as well
➢ Includes definitions
The article is available at the end of this booklet.
1
,WBI15/01 – Article potential questions Biology A Level Tutor
Entire Article Summary
Summary of the article (237 words):
Fatigue has become increasingly prevalent, particularly following the COVID-19 pandemic, where
it emerged as a core symptom of both acute infection and long covid. Once dismissed as having
no clear biological basis, fatigue is now understood as the product of an ongoing dialogue
between the body and the brain regarding available cellular energy.
Four key brain regions are central to this process: the insula and anterior cingulate cortex (part
of the interoception network), the prefrontal cortex, and the striatum. Together, these regions
perform a continuous cost-benefit analysis, weighing the energy cost of an action against its
potential reward. When energy is insufficient, motivation declines and fatigue results — not from
laziness, but from a biological resource-management calculation.
Several mechanisms can disrupt normal energy supply and cause chronic fatigue. In conditions
like ME/CFS, cells may switch to less efficient fuel sources or fail to produce adequate energy.
Brainstem dysfunction may impair oxygen delivery to muscles via the autonomic nervous system.
Microscopic blood clots, found in long covid and ME/CFS patients, can obstruct small blood
vessels and reduce oxygen transport. Additionally, chronic inflammation triggers cytokine
release, which suppresses striatal activity and conserves energy for immune function —
prolonging fatigue well beyond the initial illness.
Emerging treatments target these specific mechanisms: anti-inflammatory drugs, oxygen-
enhancing therapies, L-DOPA to boost striatal activity, transcranial magnetic stimulation, and
hyperbaric oxygen therapy. Current management strategies include pacing and cognitive
behavioural therapy, though no universal cure yet exists.
The summary of the summary is (54 words):
Fatigue results from the brain's cost-benefit analysis of available cellular energy, involving four
key brain regions. Chronic fatigue, seen in ME/CFS and long covid, stems from impaired cellular
energy production, disrupted oxygen delivery, or persistent inflammation causing cytokine
release. New treatments targeting these specific mechanisms offer hope, though none yet
provide a complete cure.
2
,WBI15/01 – Article potential questions Biology A Level Tutor
Key Take-Aways for the entire article
Key Take-Aways (You need to know and understand the following before the exam):
1. Fatigue is a Biological Process, Not a Lack of Willpower
The brain actively manages energy through a continuous cost-benefit analysis performed
by four key regions: the insula, anterior cingulate cortex, prefrontal cortex, and striatum.
When cellular energy is insufficient, the brain deliberately reduces motivation to conserve
resources. This means fatigue is not a personal weakness or laziness — it is a sophisticated,
biologically driven survival mechanism that prioritises energy for the most essential bodily
functions.
2. All Fatigue Shares a Common Brain Mechanism Despite Having Different Causes
Whether fatigue is triggered by exercise, illness, stress, long covid, or ME/CFS, it manifests
through the same brain network and produces the same fundamental experience. The
causes vary enormously — ranging from poor oxygen delivery to viral infection to
psychological stress — but the end result in the brain is remarkably consistent. As
VanElzakker's forest fire analogy illustrates, different triggers lead to the same outcome.
3. Chronic Fatigue Involves Specific, Identifiable Physical Failures in the Body
Unlike ordinary tiredness that resolves with rest, chronic fatigue involves measurable
biological disruptions. These include cells switching to less efficient fuel sources, brainstem
dysfunction impairing autonomic oxygen delivery, microscopic blood clots blocking
capillaries, and persistent cytokine-driven inflammation suppressing brain activity in the
striatum. These are real, physical, biological failures — not imagined or psychological
symptoms — and this is increasingly supported by scientific evidence.
4. Inflammation is a Central and Recurring Theme Linking Many Forms of Fatigue
Cytokines released during inflammation — whether from viral infection, long covid,
ME/CFS, or even treatment-resistant depression — directly suppress brain activity and
drive fatigue. The immune system consumes enormous amounts of ATP when activated,
leaving insufficient energy for other bodily functions. Chronic inflammation, where this
immune response never fully resolves, appears to be one of the most important and
common underlying mechanisms connecting many otherwise different fatigue conditions.
5. Treatment Must Be Tailored to the Underlying Cause, and Research is Still Evolving
There is currently no single cure for chronic fatigue. Effective treatment depends on
correctly identifying the specific biological cause in each patient — anti-inflammatory
3
, WBI15/01 – Article potential questions Biology A Level Tutor
drugs only help those whose fatigue is inflammation-driven, L-DOPA targets striatal
underactivity, and hyperbaric oxygen therapy addresses oxygen delivery problems.
Patient stories like Lisa Clock's highlight that strategies effective for healthy individuals,
such as pushing through exhaustion, can be actively harmful in chronic fatigue. Pacing and
CBT remain the most accessible current options while more targeted treatments continue
to be developed and trialled.
More Concise Key Take-Aways
1. Fatigue is not weakness → it is the brain's deliberate biological response to low cellular
energy, managed by four interconnected brain regions performing a continuous cost-
benefit analysis.
2. Regardless of its trigger — illness, exercise, or stress → fatigue always manifests through
the same brain network, producing the same fundamental biological outcome.
3. Chronic fatigue involves real, measurable physical failures → inefficient energy
production, brainstem dysfunction, microscopic blood clots, and persistent inflammation.
4. Cytokines released → during chronic inflammation directly suppress brain activity and
redirect energy to the immune system, linking ME/CFS, long covid, and depression
through a common mechanism.
5. No universal cure exists yet → treatment must target the specific underlying cause, while
pacing and CBT remain the most accessible current management options.
4
