Yes! 

Sometimes, that might take the form of the environment directly changing the genetic sequence.

• Environmental factors such as radiation, certain chemicals, or UV light can cause mutations in DNA

  • If a mutation occurs in germline cells i.e. gametes themselves (sperm or ova) or the precursor cells that give rise to them, called primordial germ cells (PGCs), it can be inherited by offspring.

  • If they occur in somatic cells, they aren’t passed on but can still affect the individual e.g. contributing to cancer development. 

• But the main way that the environment can change genes is via epigenetic changes rather than DNA mutations.

  • Epigenetics refer to the mechanisms of long-term and stable regulation of gene expression that do not involve a change to DNA sequences

  • I.e. you can actually have inheritable changes to your genome without changing the ACTG etc (woah!) 

  • Environmental factors such as diet, stress, or toxins can cause:

    • Increased DNA methylation, which inhibits transcription;

    • Decreased histone acetylation, which makes DNA more tightly coiled and less accessible for transcription;

    • Non-coding RNAs (ncRNA) can also influence gene expression. In the RNA interference (RNAi) pathway, these ncRNA can identify and destroy specific mRNA sequences = mRNA not translated into proteins

    • Such modifications can switch genes on or off and are reversible - that's important in understanding how environment contributes to all kinds of diseases (including in future generations e.g. your environment could cause epigenetic changes that effect your children and grandchildren!) 

• This is something that you might have come across in your A level studies: 

  • AQA says "Epigenetics involves heritable changes in gene function, without changes to the base sequence of DNA. Examples - increased methylation of the DNA or decreased acetylation of associated histones. In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi)."

  • Edexcel B says "Understand that gene expression can be changed by epigenetic modification, including non-coding RNA, histone modification and DNA methylation."

  • Can't seem to see much from OCR A - but epigenetics is a huge and rapidly expanding hot topic in scientific research - so do some reading about it!

Also, we know that:

• Over many generations, strong and repeated environmental pressures can lead to changes in the genotype (the DNA sequence itself) through natural selection.

• This leads to evolutionary genetic adaptation.

• E.g. if starvation is common, individuals with genes that make metabolism more efficient may survive and pass on those genes

  • This is a contributor to trends we see like the increased prevalence of type 2 diabetes in the South Asian community (check out - [1] [2]). 

Make sure to be systematic for any question like this - first describe and just say what you see, starting with the title & the axes. Then move on to suggest reasons and explanations. 

• The graph shows how the birth weights of infants in The Hague and Rotterdam changed between 1944 and 1945.

• The x-axis shows birth weight (technically mass) in kilograms, and the y-axis the progression of each 1.5 month period.

• I can see that each line on the graph corresponds to a percentile - a percentile shows how a value compares to others in a group e.g. 50th percentile (the middle line) represents the median. Half the babies weighed more than this and half weighed less. The 10th percentile line shows the weight below which the lightest 10% of babies fall.

• Across all percentiles  the birth weights drop quite sharply over the winter months and then start to rise again after a point marked as “Liberation.”

• That could be due to seasonal effects, e.g. colder weather or infection rates affecting pregnancy, but the sudden, dramatic fall seems too steep for that.

  • Might be inclined to predict something like famine 

• In reality, interviewer could tell you that this corresponds to Dutch Hunger Winter of 1944–45 -> food supplies extremely limited due to wartime blockades.

  • Pregnant women would be severely malnourished.

Coronary Heart Disease - Question 3a: 

• Coronary arteries supply oxygen and nutrients to the heart muscle. These become narrowed or blocked, usually due to a buildup of fatty deposits (atherosclerosis) on their walls.

• This reduces blood flow to the heart and can lead to problems such as angina (chest pain), heart attacks, or even heart failure.

• Good things to suggest we might have checked for e.g. recorded heart attack, hospital admissions, deaths from cardiovascular disease, history of ECG differences, reports of pain on exercising etc 

• In reality, the study looked at: presence of angina pectoris, one specific kind of ECG abnormality, and a history of coronary revascularisation (i.e. has the patient ever had a bypass operation/stent)

Coronary Heart Disease - Question 3b:

• People who were exposed to famine during early gestation had the highest prevalence of coronary heart disease later in life, almost double compared to those born before or conceived after the famine.

• The body may make permanent adjustments to cope with a lack of nutrients - possible things that students may suggest e.g. 'altered metabolism, changes in blood vessel structure, or hormone regulation.'

• Good answers will suggest that these changes are likely to correspond to epigenetic modifications i.e. changes to DNA methylation/histone modification/levels of ncRNAs in relation to genes associated with coronary artery disease e.g. vascular function. 

• Interviewer may ask a follow up - "What sort of genes do you think may be methylated?"

  • This is a complex area with ongoing research. 

    • Any plausible theory will likely be well received and show originality of thought (selection criteria).  

    • Why is it tricky to know for sure?

      • Candidates should think about the difference between association/causation - i.e. if we were to just look at the genome and see 100 different genes that are more likely to be methylated in starvation group, it's very tricky to prove which one was the driver mutation/cause of cardiovascular disease. 

      • Think about what sort of study you might need to do to prove a causation e.g. potentially do a knockout mouse model where the gene being methylated is not expressed - see whether this contributes to coronary artery disease. 

• Many possible options for a good answer here e.g. "if a gene is contributing to appetite in some way, such as a hormone that makes you feel full, then that's probably going to be downregulated" OR "atherosclerosis is a major contributor to coronary heart disease, so potentially a gene to do with the movement of cholesterol." 

• Both of those two are actually true, and I have included some information below for reference. But you wouldn't be expected to know any of that - just come up with ideas for what it might be (anything you can justify and explain is valid)! 

• • • In practice, one (of the many) changes that have been observed is hypermethylation of LEP (leptin gene)

      • Leptin is a protein hormone secreted by white adipocytes (fat cells) into the circulation

      • Leptin binds to the leptin receptor in the brain, activating signaling pathways that inhibit feeding and promote energy expenditure

    • Another difference observed is increased methylation in the promoter of the ABCA1 lipid transporter gene

      • ABCA1 helps move cholesterol and phospholipids out of cells (such as macrophages) to make HDL particles (a type of “good cholesterol") - these HDL particles carry cholesterol to the liver for removal. 

      • Patients with a mutation in ABCA1 have a rare disease called Tangier disease (and are at risk of coronary artery disease)

      • If we are methylating this (and so it's not expressed), you can imagine why it would lead to a similar outcome

• Adaptations may help the baby survive in the womb but increase the risk of heart disease in adulthood, especially if the person later grows up in an environment where food is abundant.

Coronary Heart Disease - Question 3c:

• Likely to be some sort of predictive adaptive mechanism.

• If a fetus develops in a low-nutrient environment, it can be anticipated that food will be scarce after birth, with metabolism adjusted to store energy efficiently and conserve resources. 

  • This would be a beneficial adaptation in an environment where food really is scarce, and so something that there is a selection pressure in favour of. 

  • Quick reminder of the process (AQA biology specification): "Random mutation can result in new alleles of a gene. Many mutations are harmful but, in certain environments, the new allele of a gene might benefit its possessor, leading to increased reproductive success. The advantageous allele is inherited by members of the next generation. As a result, over many generations, the new allele increases in frequency in the population.  Natural selection results in species that are better anatomically/physiologically/behaviourally adapted to their environment."

• If the environment later becomes nutrient-rich, the same adaptations can become harmful and leading to obesity, diabetes, and heart disease - i.e. maladaptive in modern societies. 

--- Further reading if interested --- 

There are lots of examples like this, where historic selective advantages are believed to correspond to contemporary disease.

E.g.

SURVIVAL THREAT                                SELECTIVE ADVANTAGE                                          CONTEMPORARY DISEASE

Combat starvation     --->     Energy conservation      --->      Obesity/metabolic syndrome

Combat dehydration     --->      Fluid and electrolyte conserve     --->      Hypertension

Combat injurious agents     --->      Potent immune reaction      --->     Autoimmunity/Allergy

Anticipate adversaries      --->     Arousal/fear     --->      Anxiety/insomnia

Minimize exposure to danger     --->      Social Withdrawal      --->     Depression

Prevent tissue strain/damage      --->     Retain tissue integrity      --->      Pain and fatigue syndromes

Prevent social bond disruption      --->     Retain social integrity      --->     Dehumanisation behaviors (i.e. psychopathy, narcissism, racism, fanaticism, chauvinism, etc.)

Figure 3: What are the trends?

• Figure 3 shows us the rate of return on investment in human capital (such as healthcare spending) is highest during the earliest stages of life, especially early childhood and the prenatal period.  

• In the context of healthcare, we know that the brain, immune system, and metabolism are still developing and highly plastic in the prenatal and early childhood periods, as is exemplified by the FOAD hypothesis. 

• Any interventions in this phase of a person's life are likely to shape health/behaviour across a lifetime, and therefore have a much larger effect. 

• When we aim to target these chronic diseases in the prenatal period/early childhood, what we are looking at is prevention. Taking a preventative approach to disease is going to be cheaper/more effective than trying to treat once this is established. 

  • For example, if we can improve the maternal diet or reducing childhood obesity, this is likely to prevent cardiovascular disease decades later. It is also relatively cheap to do. 

  • In contrast, if we treat adults with stents, bypass surgery, or GLP-1 agonists - this is not only expensive, but also less effective, as it only treats the symptoms. 

How should we spend the £1 billion?

(Naturally, there is no single right answer to a question like this. Any point that is justified/well-explained will likely be valid. It's important to give a balanced perspective.)

• Department of Health and Social Care (which funds NHS England) has a budget well over £200 billion each year

  • While £1 billion may sound like a lot of money, this is <0.5% of the NHS budget each year, and there will likely be many competing challenges.

• If possible, we would aim to spend the money on early and primary prevention rather than treatment.

  • Key word 'primary prevention' -> targeting the healthy population to prevent disease before it happens.

  • Much of the NHS spending currently goes into managing established disease - these treatments come late in the disease pathway and are very costly per patient,

• There is evidence to show that interventions in early life (including the prenatal period) can strongly influence health in the long term. Some good options could be:

  • Prenatal care and maternal health programs -> better nutrition, regular check-ups, smoking cessation, and mental health support for expectant mothers.

  • Early childhood interventions -> health visitors, vaccination programmes, and nutrition education for parents.

  • Public health measures in schools -> promoting physical activity and healthy diets.

• These measures would help to prevent chronic disease before it starts and address root causes.

  • Spending earlier = higher return on investment, potentially reduced costs for the NHS in the long run 

• Must give a balanced perspective -> while preventative measures may provide the most value and return on investment in the long run, it is also important to consider any urgent, short-term needs in light of e.g. extended waiting lists/A&E crisis. 

  • Also worth considering whether funding research/technology could provide even more benefit in the long term by e.g. discovering new and/or more cost-effective treatments and therapies. 

Good answers will be able to refer to healthcare inequalities - early investment in preventative measures will improve health equity across the population.

• • I would recommend (for both MMI and Oxbridge purposes) to do some reading into the conclusions of the Marmot Review - some key findings: 

    • in England, those living in the least wealthy neighbourhoods on average die 7 years earlier than people living in the wealthiest, spending an average of 17 more years of life in disability.

    • The review found a social gradient of health inequalities - the lower one's social and economic status, the poorer one's health is likely to be.

• An ECG (electrocardiogram) records the electrical activity of the heart across repeated cardiac cycles.

  • The figure is a graph of voltage versus time of the electrical activity of the heart, measured using electrodes that are placed against the skin

  • Electrodes detect the small electrical changes resulting from of cardiac muscle depolarisation followed by repolarisation during each cardiac cycle 

Optional Extra Info: 

• The electrocardiogram does not measure voltage inside heart cells.

• Instead, it detects electrical currents in the extracellular space = the region outside the cells.

• These currents arise when some areas of the myocardium are depolarised (excited) and others are still resting (polarised).

• Imagine a single heart muscle cell depolarising:

  • Na+ ions will rush in, making the inside of the cell more positive

  • That means the outside of the cell is going to be negative relative to its surroundings 

  • A dipole or separation of charge will be created between depolarised and resting regions

    • In physics, a dipole moment is conventionally defined as pointing from the negative to the positive charge. 

  • As the wave of depolarisation moves through the myocardium, the dipole is going to shift.

• This moving dipole is going to generate extracellular current flow

• The ECG is going to measure the flow of extracellular current 

  • If the positive charge is moving towards a positive electrode, the ECG trace shows an upward (positive) deflection.

  • If it moves away, you get a downward (negative) deflection.

  • The size of the deflection indicates magnitude of current flow, which corresponds to the scale of the wave of depolarisation in the heart.