6.3.1 Health and disease

What health means

1. Health is a state of complete physical, mental and social wellbeing, so it is never measured only by whether a person is free of illness.
2. Good physical health means the cells, tissues, organs and organ systems of the body are all working as they should.
3. Good mental health means a person can think clearly, manage their emotions and cope with the ordinary demands of daily life.
4. Good social wellbeing means having secure housing, enough food, safe water and supportive relationships with other people.
5. A disease is a condition in which part of an organism stops working normally, and the changes this produces are called symptoms.
6. A person can be carrying no pathogen at all and still be in poor health, for example someone living in cold damp housing on a diet that is short of protein and vitamins.
   1. The reverse also holds, because a person whose long term condition is well controlled by medicine can be in good general health.

Factors that affect health

1. Diet affects health because the body needs energy, protein, vitamins and mineral ions to build tissues and repair damage.
2. Stress affects health because long periods of it disturb sleep, appetite and mood, which makes existing conditions harder to control.
3. A person's life situation affects health, including their housing, income, working conditions and whether clean water and sanitation are available.
4. Access to medical care affects health because a disease that is diagnosed and treated early usually causes far less damage than one left untreated.
5. Regular physical activity keeps the heart, lungs and muscles working efficiently and helps hold body mass in a healthy range.

Communicable and non-communicable diseases

1. Every disease belongs to one of two groups, and the group depends on a single question: can it be passed to another organism?
2. A communicable disease is caused by a pathogen, a microorganism such as a virus, bacterium, fungus or protist, which reproduces inside or on the host.
   1. Because the pathogen itself can move between organisms, the disease can spread through a population.
3. Communicable diseases of humans include measles, influenza, cholera, tuberculosis and athlete's foot.
4. Plants suffer communicable diseases too, for example tobacco mosaic virus in tomato plants and crown gall disease in fruit trees.
5. A non-communicable disease is not caused by a pathogen, so nothing can move from a sick organism to a healthy one and it cannot be passed on.
6. Non-communicable diseases include coronary heart disease, type 2 diabetes, most cancers, arthritis and asthma.

Comparing the two types

1. A communicable disease usually appears quickly, often within days of the pathogen entering the body, because the pathogen reproduces rapidly.
2. A non-communicable disease usually develops slowly over years, so symptoms may appear long after the cause first began acting.
3. A communicable disease can often be treated by killing the pathogen, for example by using antibiotics against a bacterium.
4. A non-communicable disease cannot be cured by killing a pathogen, because there is no pathogen present to kill.
5. The number of cases of a communicable disease can rise sharply in weeks, whereas the number of cases of a non-communicable disease changes slowly as diets, activity levels and the age of a population change.

Deficiency diseases

1. A deficiency disease is one type of non-communicable disease, caused by a diet that is short of a particular nutrient or mineral ion.
2. A shortage of carbohydrate removes the body's main fuel for respiration, so it breaks down its own stored fat and then its muscle protein to release the energy it needs.
   1. The person loses body mass, tires easily and feels cold, because less energy is being released to keep the body warm and active.
   2. When the shortage of energy is severe and long lasting in a young child the result is marasmus, in which the fat stores and muscles are wasted away and the child is far below the expected body mass for their age.
3. A shortage of protein starves the body of the amino acids it needs to build new cells, repair damaged tissue and make enzymes and antibodies.
   1. Growth slows or stops in children, wounds heal slowly, and infections take hold more easily because fewer antibodies can be made.
   2. Severe protein shortage causes kwashiorkor, whose most recognisable sign is a swollen abdomen, caused by fluid leaking out of the blood and collecting in the tissues.
4. A shortage of lipids leaves the body without its densest energy store, without the insulating fat layer under the skin and without the raw material for cell membranes.
   1. The person loses heat quickly and cannot keep a steady body temperature in the cold, and the skin becomes dry and scaly.
   2. Vitamins A, D, E and K dissolve in fat rather than in water, so a diet with almost no lipid in it also leads to a shortage of those vitamins.
5. A shortage of dietary fibre matters even though fibre is not digested and releases no energy, because it is the bulk that gives the gut something to grip.
   1. Fibre holds water and keeps the contents of the intestine soft and bulky, so the muscles of the gut wall can squeeze them along by peristalsis.
   2. Without enough fibre the contents move slowly, more water is absorbed from them, and the result is constipation and a raised risk of bowel disease.
6. Too little vitamin C causes scurvy, in which the gums bleed and wounds heal slowly, because vitamin C is needed to make the protein collagen.
7. Too little vitamin D or calcium causes rickets in children, because the leg bones stay soft and bend under the weight of the body.
8. Too little iron causes anaemia, because iron is needed to make haemoglobin, so the blood carries less oxygen and the person tires quickly.
9. Every one of these conditions is corrected by returning the missing nutrient to the diet, which is further evidence that no pathogen is involved and that none of them can be passed on.

6.3.2 Interactions between diseases

How one disease leads to another

1. Diseases do not act in isolation, because having one disease often makes a second disease more likely to develop or more severe when it does.
2. When a person has two or more diseases at the same time this is called comorbidity, and the combination is usually harder to treat than either disease alone.
3. There are four routes by which one disease opens the door to another.
   1. Damage to the immune system leaves the body unable to destroy pathogens it would normally deal with easily.
   2. A virus infecting host cells can disturb how those cells divide and so trigger a cancer.
   3. An immune response to a pathogen can leave the body reacting to harmless substances afterwards, producing an allergy.
   4. Severe physical illness can lead to mental illness, because pain, disability and uncertainty all take a toll.

HIV and tuberculosis

1. HIV, the human immunodeficiency virus, infects a group of white blood cells called helper T lymphocytes, also known as CD4 cells, which coordinate the body's response to infection.
2. The virus reproduces inside these cells and destroys them, so the number of CD4 cells in the blood falls steadily over several years while the number of virus particles rises.
3. Soon after infection the person has a short flu-like illness, after which they may feel well for years even though the virus is still reproducing.
4. Once the CD4 count drops far enough the immune system can no longer control pathogens, and the person is said to have AIDS, acquired immune deficiency syndrome.
5. Tuberculosis is a communicable disease of the lungs caused by the bacterium Mycobacterium tuberculosis, which spreads in droplets breathed out by an infected person.
6. In a healthy person white blood cells surround the bacteria and seal them inside small lumps of tissue in the lung, so the infection stays dormant and causes no symptoms.
7. In a person with HIV there are too few working lymphocytes to hold the bacteria in place, so the dormant infection breaks out into active tuberculosis with a persistent cough, weight loss and fever.
   1. This is why tuberculosis is the infection that most often kills people living with untreated HIV, even though HIV itself destroys no lung tissue.
8. Antiretroviral therapy slows the reproduction of HIV, so the CD4 count stays high, the immune system keeps working and the risk of tuberculosis falls sharply.

HPV and cervical cancer

1. Human papillomavirus, usually shortened to HPV, is passed on by skin to skin contact during sexual activity and infects the cells lining the cervix.
2. Most HPV infections are cleared by the immune system within about two years and cause no lasting harm.
3. A few strains of HPV insert their genetic material into the DNA of the cervix cells and make proteins that switch off the controls on cell division.
4. The infected cells then divide uncontrollably, forming a mass of abnormal cells that can develop over many years into cervical cancer.
5. The cancer itself is a non-communicable disease, because the tumour cannot pass to another person, yet the virus that started it is communicable.
6. Cervical screening finds abnormal cells before they become cancerous, and vaccination against HPV before a person becomes sexually active stops the infection that starts the whole sequence.

Other interactions between diseases

1. The immune response raised against a pathogen can leave the body over-reacting to harmless substances afterwards, which is why some children develop asthma or skin rashes following a viral infection of the airways.
2. Physical damage to a barrier lets pathogens reach tissues that are normally sealed off, so a deep wound or a burn is frequently followed by a bacterial infection of the skin.
3. A non-communicable disease can also make a communicable one more likely, because poorly controlled diabetes reduces blood flow to the feet and slows healing, so small wounds there become infected.
4. Long or severe physical illness raises the risk of depression and other mental illness, because of continuing pain, loss of independence and the strain of an uncertain future.
5. For all these reasons a doctor treats the whole patient rather than one illness in isolation, and controlling the first disease is often the most effective way of preventing the second.

6.3.3 Spread of communicable diseases

How pathogens pass between hosts

1. Transmission is the passing of a pathogen from an infected host to an uninfected organism, and without it a communicable disease dies out with its host.
2. A pathogen can only reproduce inside or on a host, so reaching a new host before the old one recovers or dies is essential to its survival.
3. The route a pathogen uses depends on where it lives in the body, because a pathogen in the gut leaves in the faeces while one in the lungs leaves in exhaled droplets.
4. The main routes are direct contact, body fluids, the air, water, food and vectors, and most pathogens use one or two of them rather than all six.

Direct contact and body fluids

1. Direct contact spreads a pathogen when infected skin touches healthy skin, or when both people touch the same surface.
   1. Athlete's foot is picked up from wet changing room floors and shared towels, where the fungus survives in warm damp conditions.
2. Body fluids carry pathogens that cannot survive long in the open air, including blood, semen, vaginal fluid and breast milk.
3. HIV passes between people during unprotected sexual intercourse, through needles shared between drug users, in a transfusion of infected blood, and from a mother to her baby during pregnancy, birth or breastfeeding.
4. A pathogen that needs body fluids to travel cannot be caught from sharing a cup, a toilet seat or a hug, because it dries out and dies once outside the body.

Air, water and food

1. Airborne pathogens travel in the tiny droplets of liquid released when an infected person coughs, sneezes or talks.
   1. A single sneeze can release many thousands of droplets, which are then breathed in by anyone standing nearby or settle onto surfaces that are later touched.
   2. Influenza, measles and tuberculosis all spread this way, which is why they move quickly through crowded indoor spaces.
2. Water-borne pathogens leave the body in faeces and enter drinking water that has been contaminated with sewage.
   1. Cholera spreads in this way, so outbreaks follow floods, earthquakes and any other event that mixes sewage with the water supply.
3. Food-borne pathogens are swallowed in food that has been undercooked, stored too warm or handled with dirty hands.
   1. Salmonella grows in raw poultry and eggs, and also transfers onto salad when the same board or knife is used for both.

Vectors and spread between plants

1. A vector carries a pathogen from one host to another without developing the disease itself, so it acts as a living delivery system.
2. A female mosquito takes up the malarial protist when it feeds on the blood of an infected person, then injects it into the next person it bites.
3. Plants have no immune system and cannot move away from infection, so pathogens reach them by several distinct routes.
   1. Insects such as aphids and whitefly act as vectors, pushing their mouthparts into the phloem of one plant after another and carrying viruses with them.
   2. Wind carries the spores of fungal pathogens such as powdery mildew across whole fields in a single day.
   3. Rain splashes spores from infected soil and fallen leaves upwards onto healthy foliage.
   4. Direct contact passes pathogens between touching leaves, and gardeners transfer them on unsterilised secateurs, boots and hands.
   5. Infected seeds, tubers and cuttings carry a pathogen straight into a new crop before it has even germinated.

Reducing and preventing spread

1. Hygiene removes pathogens before they reach a new host, because soap lifts them off the skin and running water washes them away.
   1. Disinfectants applied to kitchen worktops, door handles and hospital surfaces kill the pathogens that survive there between touches.
2. Isolating infected people keeps them apart from others for as long as they remain infectious, so there is nobody nearby for droplets or contact to reach.
3. Controlling vectors cuts transmission by removing the carrier, using insecticides, draining the standing water where mosquitoes breed and sleeping under treated nets.
4. Treating water and sewage breaks the water-borne route, because filtration and chlorination kill the pathogens before the water is drunk.
5. Safe food handling means cooking food right through, chilling it below the temperature at which bacteria reproduce quickly, and keeping raw meat away from food that will be eaten uncooked.
6. In crops, growers remove and burn infected plants, rotate crops so a soil pathogen loses its host, sterilise tools between plants, control insect vectors and plant resistant varieties.

Vaccination and herd immunity

1. A vaccinated person is already immune, so a pathogen that reaches them is destroyed before it can reproduce in large numbers.
2. Because the pathogen never builds up inside that person, they do not pass it on, and the chain of transmission stops at them.
3. As the proportion of vaccinated people rises, each infected person meets fewer and fewer susceptible people, so the average number of new infections caused by each case falls.
4. Once that average drops below one new case per infected person the outbreak shrinks instead of growing, and the unvaccinated are protected as well, which is herd immunity.
5. The proportion needed depends on how infectious the pathogen is, and measles is so infectious that roughly $95\%$ of a population must be vaccinated.
6. Herd immunity matters most for babies too young to be vaccinated and for people whose immune systems are damaged, since neither group can be protected directly.
7. If the vaccination rate slips below the threshold the pathogen begins to spread again, which is why outbreaks reappear in areas where uptake has fallen.

Working with numbers of cases

1. A raw count of cases cannot be compared between two places of different size, so figures are reported as an incidence per fixed number of people.
2. Incidence is calculated using $incidence=\frac{number\; of\; new\; cases}{population}\times 100000$.
3. The number of cases expected in another population is then estimated by reversing the calculation, multiplying the incidence by that population and dividing by $100000$.
4. Numbers of pathogens grow in the same exponential way, because a bacterium divides in two by binary fission, giving $N=N_0\times 2^n$ where $n$ is the number of divisions.
   1. Very large or very small values are written in standard form, so $512000$ bacteria is recorded as $5.12\times 10^5$.
5. A sharp rise in incidence above the level normally expected in an area is described as an epidemic, and one that spreads across several countries is a pandemic.

6.3.4 Common infections and diseases

The four groups of pathogen

1. Communicable diseases of humans and of plants are caused by four groups of pathogen, and each group damages its host in a characteristic way.
2. Viruses are not cells, so they take over the machinery of a host cell to make copies of themselves and the cell is destroyed as the new virus particles are released.
3. Bacteria are cells that reproduce rapidly inside the body and damage tissues mainly by releasing poisonous toxins.
4. Fungi grow threads called hyphae into the tissues of the host and release enzymes that digest those tissues so the fungus can absorb the products.
5. Protists are single-celled organisms that live as parasites inside the host, and most of them rely on a vector to carry them from one host to the next.

Influenza, a viral infection

1. Influenza is caused by the influenza virus, which infects the cells lining the nose, throat and lungs.
2. The virus attaches to a lining cell, enters it and forces the cell to build hundreds of new virus particles, which are released as the cell bursts and dies.
   1. Destroying the lining strips away the mucus and cilia that normally trap and sweep out dirt, which is why a bacterial chest infection often follows influenza.
3. The symptoms are a sudden high temperature, aching muscles, headache, a dry cough and severe tiredness that lasts for a week or more.
4. The virus is spread in droplets released when an infected person coughs or sneezes, and on hands and surfaces those droplets land on.
5. There is no antibiotic treatment, so recovery depends on the immune system, and the yearly vaccine is offered to people most at risk of serious illness.

Cholera, a bacterial infection

1. Cholera is caused by the bacterium Vibrio cholerae, which is swallowed in water or food contaminated by the faeces of an infected person.
2. The bacteria that survive the stomach acid reach the small intestine, attach to its lining and multiply there in huge numbers.
3. They release a toxin that acts on the lining cells and makes them pump salts out of the blood and into the gut.
4. The contents of the gut are now a more concentrated solution than the blood, so water moves out of the blood and into the gut by osmosis through the partially permeable cell membranes.
5. The gut fills with fluid, producing the severe watery diarrhoea that is the main symptom, and an adult can lose several litres in a few hours.
6. Losing water and salts this quickly causes dehydration, the blood volume falls, and without treatment the person can die within a day.
7. Treatment is an oral rehydration solution of clean water with salts and sugar dissolved in it, because the sugar helps the salts and therefore the water to be absorbed back across the gut wall.

Athlete's foot, a fungal infection

1. Athlete's foot is caused by a fungus that grows in the warm moist skin between the toes, conditions it needs to reproduce.
2. Its hyphae grow into the dead outer layer of the skin and release enzymes that digest the protein keratin, and the fungus absorbs the products.
3. The damaged skin becomes itchy, red, dry and cracked, and it flakes away carrying fungal spores with it.
4. Those flakes are how the infection spreads, which is why it passes between people on wet changing room floors, in shared showers and on shared towels.
5. It is treated with an antifungal cream or powder, and kept away by drying between the toes and wearing sandals in communal showers.

Sexually transmitted infections

1. A sexually transmitted infection is passed on during sexual contact, because the pathogens involved survive only in the moist conditions of body fluids.
2. HIV is a virus that causes a short flu-like illness and then infects and destroys the lymphocytes that coordinate the immune response.
   1. Once too few of those cells remain, the body can no longer fight off other pathogens and the person is said to have AIDS.
   2. Antiretroviral drugs hold the virus at very low levels so the immune system keeps working, but they do not remove the virus from the body.
3. Chlamydia is caused by a bacterium and often produces no symptoms at all, so it is passed on unknowingly for months.
   1. Untreated it scars the oviducts and sperm ducts, which is why it is a common cause of infertility, and it is cured with antibiotics if it is found.
4. Gonorrhoea is also bacterial and gives a thick yellow or green discharge and pain on urinating, and strains resistant to the usual antibiotics are now common.
5. Spread of all three is reduced by using a condom as a barrier, by screening people who have no symptoms, by treating partners at the same time and by not sharing needles.

Tobacco mosaic virus in plants

1. Tobacco mosaic virus, usually shortened to TMV, infects tobacco, tomato, pepper and more than a hundred other species.
2. It gives the leaves a distinctive mottled mosaic pattern of light green, yellow and dark green patches, and the leaves are often crinkled or narrowed.
3. The pale patches contain far less chlorophyll, so they absorb less light, the rate of photosynthesis falls and the plant makes less glucose.
   1. With less glucose available for respiration and for building new tissue, growth is stunted and the crop yield drops.
4. TMV is spread by contact between leaves and on the hands, clothing and tools of anyone working among the plants.
5. The virus is unusually stable and survives for years in dried plant debris and in the soil, so infected material must be removed and destroyed rather than dug in.

Barley powdery mildew

1. Barley powdery mildew is caused by the fungus Erysiphe graminis, one of the most damaging diseases of cereal crops.
2. White fluffy pustules of fungal hyphae and spores appear on the upper surface of the leaves, later turning grey and brown.
3. Fine hyphae push through the cell wall into the epidermal cells and absorb sugars directly from them, so food the plant made for itself is taken by the fungus.
4. The white covering also blocks light from reaching the chloroplasts underneath, which lowers the rate of photosynthesis still further.
   1. Leaves yellow and die early, the grain that forms is small and light, and yields can fall by a fifth or more in a badly infected field.
5. Spores are carried long distances on the wind, and the disease builds up fastest in mild damp weather and in crops sown thickly.
6. Growers control it with fungicide sprays, by sowing resistant varieties and by avoiding heavy nitrogen fertiliser, which produces the soft leafy growth the fungus prefers.

Crown gall disease

1. Crown gall disease is caused by the soil bacterium Agrobacterium tumefaciens, which attacks fruit trees, roses, grapevines and many other woody plants.
2. The bacterium lives in the soil and can only get in through a wound, such as the damage done by a spade, a graft or frost at the base of the stem.
3. Once inside it transfers a piece of its own DNA into the DNA of the plant cells around the wound.
4. That inserted DNA switches on uncontrolled cell division, so the infected cells keep dividing and form a swollen lumpy growth called a gall.
5. The disorganised gall tissue crushes and interrupts the xylem and phloem running through the stem, so water and dissolved sugars can no longer be transported properly.
   1. The plant above the gall is left short of water and minerals, so it grows poorly, wilts in dry weather and may die.
6. Control depends on prevention, using clean planting stock, sterilised tools and careful handling so that the roots and stem base are not wounded.

6.3.5 Physical plant defence responses

Why plants need physical defences

1. Plants have no circulating white blood cells and make no antibodies, so they cannot hunt down a pathogen once it is inside them.
2. A plant is also rooted in one place, so it cannot move away from infected neighbours or from the insects carrying disease.
3. Its defences are therefore built into its structure, and a physical defence is a barrier that stops the pathogen reaching living tissue in the first place.
4. To infect a leaf a pathogen must cross two barriers in turn, first the waterproof layer on the outside and then the wall around each cell.

The waxy cuticle

1. The waxy cuticle is secreted by the epidermal cells and forms a continuous waterproof sheet over the upper and lower surfaces of every leaf.
2. Because it repels water, rain runs straight off instead of sitting on the surface as a film.
   1. Fungal spores need a film of surface water to germinate, and many bacteria need it to swim towards a stoma, so removing the water removes their route in.
3. The wax is also a solid barrier in its own right, and a fungal thread cannot push through an intact cuticle to reach the epidermal cells beneath.
4. Plants growing in exposed or dry places build a much thicker cuticle, which is why a holly leaf feels hard and glossy while a lettuce leaf tears easily.
5. The cuticle is broken by hail, wind damage, grazing and careless pruning, and almost every leaf infection begins at a break of this kind.

Cell walls

1. Every plant cell is enclosed in a cellulose cell wall, so a pathogen that gets past the cuticle meets a second barrier at every single cell.
2. Cellulose is built from long chains bundled into fibres that criss-cross in layers, which makes the wall extremely strong for its thickness.
   1. A fungal thread grows by pushing forwards with great force, and the cross-linked fibres of the wall resist that pressure.
3. The wall also keeps the pathogen away from the cytoplasm, and a virus or bacterium that cannot reach the cytoplasm cannot reproduce.
4. Some walls are strengthened further with lignin, a hard waterproof substance found in xylem vessels and in the woody parts of stems and roots.
   1. Lignified walls are much harder for enzymes to digest, so a pathogen that dissolves its way through ordinary cell walls is stopped by them.
5. A plant can also lay extra material down inside the walls around a wound, which thickens them and seals the infected area off from healthy tissue.

Bark and layers of dead cells

1. The stems and roots of woody plants are covered by bark, which is made of layers of dead cells whose walls are soaked in a waterproof substance.
2. These cells contain no cytoplasm, so a virus or bacterium that reaches them finds nothing it can use to reproduce.
3. Bark is shed continuously in flakes and plates, so any pathogen that has settled on the outside is carried away before it can work inwards.
4. Deciduous trees use the same trick on a yearly cycle, dropping every leaf in autumn and taking the season's fungal infections down with them.
   1. The tree then opens fresh, uninfected leaves in spring, which is why gardeners are told to rake up and burn fallen leaves rather than leave them under the tree.

Defences against animals that damage plants

1. Thorns, spines and stinging hairs make a plant painful to eat, so a herbivore moves on to something easier.
   1. This protects the plant against disease as well as against grazing, because every bite leaves a wound through which pathogens can enter.
2. Dense hairs on a leaf surface hold small insects away from the epidermis, so an aphid carrying a virus cannot reach the phloem to feed.
3. Leaves that droop or curl when touched, as in the sensitive plant, throw feeding insects off and make the plant look smaller and less worth eating.
4. Closing the stomata shuts the one opening in the cuticle, which denies pathogens their easiest route into the leaf.
5. Mimicry works by appearance rather than by force, and some passion flower species grow small yellow spots that look like butterfly eggs.
   1. A female butterfly avoids laying on a leaf that already appears to carry eggs, so no caterpillars hatch there and the leaf is never eaten.
6. Almost no plant relies on a single defence, and a rose bush combines a waxy cuticle, cellulose walls, woody stems and thorns at the same time.

6.3.6 Chemical plant defence responses

How chemical defences work

1. A chemical defence is a substance the plant makes that attacks the pathogen itself, rather than a barrier that keeps the pathogen outside.
2. This matters because a barrier is useless once it has been broken, and a chemical can still act on a pathogen that has already got in.
3. Some of these substances are present in the tissues all the time, so a pathogen meets them the moment it arrives.
4. Others are made only after the plant detects damage or infection, which saves the energy and raw materials that making them all year would cost.
5. Because the substances are soluble they diffuse through the tissue around the infected area, so they reach the pathogen wherever it has spread to.

Antibacterial and antifungal substances

1. Antibacterial substances damage the cell wall or the cell membrane of a bacterium, so it either bursts or can no longer take in what it needs to reproduce.
   1. Garlic produces allicin when its tissue is crushed, and mint and witch hazel produce oils that act in the same way.
2. Antifungal substances stop fungal threads growing into the tissue, usually by breaking down the membranes of the growing hyphae.
   1. Oat roots contain a substance that punches holes in fungal membranes, and the bark of many trees is rich in compounds that do the same.
3. Many plants make both kinds at once, which is why plant tissue rots far more slowly while it is alive than it does after it dies.
4. The effectiveness of an extract is compared by growing bacteria on agar and measuring the clear zone of inhibition it produces, since a larger zone means the substance has diffused further and still killed bacteria.

Chemicals that deter animals

1. Poisons kill or sicken an animal that eats the plant, so the rest of that population learns to leave the species alone.
   1. Foxglove leaves contain a substance that disturbs the rhythm of the heart, deadly nightshade berries contain one that blocks nerve signals, and tobacco leaves contain nicotine, which is toxic to insects.
2. Bitter-tasting chemicals work without harming the animal, because a mouthful that tastes unpleasant is spat out and the plant is left alone.
   1. Tannins in oak and tea leaves bind to proteins in the mouth and gut, which makes the leaf taste harsh and makes its protein harder to digest.
3. Fewer animals feeding means fewer holes bitten in the leaves, and since almost every infection starts at a wound this cuts the rate of disease as well.
4. Some plants release scent chemicals into the air as soon as a caterpillar starts to feed, and these attract wasps that lay their eggs in the caterpillar.

Plant defence chemicals as medicines

1. A substance that kills a bacterium in a leaf may also kill the same bacterium in a person, so plant defences have long been a starting point for medicines.
2. Aspirin is based on a compound from willow bark, where the plant uses it as part of its response to infection, and it is now used to relieve pain and fever.
3. Quinine comes from the bark of the cinchona tree and was the first effective treatment for malaria.
4. Digitalis, the foxglove poison that deters herbivores, is used in carefully measured doses to steady a failing heart.
5. The dose is what separates a poison from a medicine, which is why these substances are extracted, purified and measured precisely rather than taken as raw plant material.

6.3.7 Detecting and identifying plant diseases

Signs that a plant is diseased

1. Stunted growth is the commonest sign, because a diseased plant diverts resources away from making new tissue or has lost leaf area for photosynthesis.
2. Spots on the leaves mark patches of tissue the plant has killed off and sealed away to stop a fungal or bacterial infection spreading.
3. Areas of decay appear where a pathogen has digested the tissue, leaving it soft, brown and rotting, most often on fruit, stems and roots.
4. Abnormal growths such as galls form when a pathogen makes the plant's own cells divide out of control.
5. Malformed stems and leaves appear twisted, curled or narrowed when a virus disturbs the way new tissue develops.
6. Discolouration ranges from the mottled mosaic of a viral infection to the white powdery coating of a fungus and the general yellowing of leaves that are dying back.
7. Visible pests such as aphids, caterpillars and whitefly are a sign in themselves, since they both damage the plant and carry pathogens between plants.

Diagnosis in the field

1. The first step is careful observation with the naked eye and a hand lens, recording which parts of the plant are affected and how badly.
2. The pattern across a field is as informative as the symptom itself, because an infection usually starts in one patch and spreads outwards over the following weeks.
   1. A problem that appears evenly across the whole crop at once points instead to the soil or the weather, since a pathogen needs time to travel.
3. Whether the oldest or the youngest leaves are affected first narrows the possibilities further, and so does the position of the marks on each leaf.
4. The symptoms are then matched against a gardening manual, an identification key or an online database of photographs of known plant diseases.
5. A hand lens or a portable microscope shows the structures that a photograph cannot, such as fungal threads, masses of spores and the insects feeding on the underside of a leaf.
6. A field testing kit gives a chemical answer on the spot, using a strip carrying antibodies that bind to the pathogen and produce a coloured line within minutes.
   1. Field methods are quick and cheap and need no laboratory, but they can mistake one disease for another that looks similar, so a doubtful result is sent away for testing.

Identification in the laboratory

1. A sample of infected tissue sent to a laboratory can be tested for the pathogen itself, which gives a certain answer rather than a likely one.
2. Antigen testing works because every pathogen carries antigens on its surface whose shape is unique to that species.
   1. Antibodies with a binding site complementary to that antigen are produced, and each one is attached to a coloured dye or to an enzyme that produces a colour.
   2. Ground-up plant tissue is added to a well or a test strip coated with those antibodies, and anything that does not bind is washed away.
   3. A colour appears only if the antigen was present to hold the antibodies in place, so a colour change identifies the pathogen.
3. DNA testing works because the genetic material of each pathogen has a base sequence found in no other organism.
   1. DNA is extracted from the plant sample and copied many times over, so that even a trace of pathogen DNA becomes enough to detect.
   2. Short labelled lengths of single-stranded DNA called probes are added, and each probe has a base sequence complementary to part of the pathogen's DNA.
   3. A probe binds only to the matching sequence, so a signal from the label shows that the pathogen's DNA is in the sample.
4. DNA testing can separate two strains that look identical under a microscope, which matters when only one of them is resistant to the chemical the grower plans to use.
5. A laboratory can also grow the pathogen from the sample on agar and examine its spores at high magnification, which is slower than a test kit but shows the living organism.
6. Laboratory methods are accurate and specific but cost more and take days, so a crop is usually screened in the field and only doubtful cases are sent away.

Ruling out a mineral deficiency

1. An unhealthy plant is not always an infected one, because a shortage of a mineral ion in the soil produces symptoms that look very like disease.
2. A shortage of nitrate ions gives stunted growth and pale older leaves, because nitrate is needed to make the amino acids from which proteins are built.
   1. Without enough protein the plant cannot make new cells, so growth slows and the plant stays small.
3. A shortage of magnesium ions causes chlorosis, in which the leaves turn yellow, because magnesium is a component of chlorophyll.
   1. With less chlorophyll the leaf absorbs less light, the rate of photosynthesis falls and the plant grows poorly even in bright conditions.
4. Three things separate a deficiency from an infection: it affects the whole crop evenly, there are no spots, spores or growths to find under a lens, and it does not spread outwards over time.
5. The diagnosis is confirmed by testing the soil for the ion in question, and by adding a fertiliser containing it and seeing whether new growth comes through green and healthy.

6.3.8 White blood cells and platelets

Defence cells in the blood

1. Blood is made of a liquid called plasma carrying red blood cells, white blood cells and platelets.
2. Red blood cells carry oxygen, while white blood cells and platelets are the parts of the blood that defend the body against pathogens.
3. White blood cells are much less common than red blood cells, with roughly one white blood cell for every $600$ red blood cells in a healthy person.
4. Unlike red blood cells, every white blood cell has a nucleus, and the shape and size of that nucleus is one way of telling the different types apart.
5. The number of white blood cells rises during an infection, because the body makes more of them to fight the pathogen.
6. There are two main types of white blood cell, the phagocytes and the lymphocytes, and each has a structure suited to a different job.
7. Platelets are not whole cells but tiny fragments of cells, and their job is to start the formation of a blood clot when a blood vessel is damaged.
8. A cell is adapted to its function when its structure makes it able to carry out that function well, so every feature described below should be linked to what it lets the cell do.

Phagocytes

1. A phagocyte destroys pathogens by phagocytosis, which means it takes a pathogen inside itself and digests it.
2. Phagocytes are non-specific, so the same phagocyte will engulf a bacterium, a virus, a fungal spore or any other cell it recognises as foreign.
3. Phagocytosis happens in a fixed sequence of steps.
   1. The phagocyte is attracted towards the pathogen by chemicals released by the pathogen and by damaged tissue.
   2. The phagocyte's cell membrane flows around the pathogen until the pathogen is completely engulfed inside a small bag of membrane called a vacuole.
   3. Small sacs called lysosomes fuse with the vacuole and release digestive enzymes onto the pathogen.
   4. The enzymes break the pathogen down into small harmless molecules, which the phagocyte absorbs or releases.
4. Each feature of a phagocyte is linked to one of these steps.
   1. A flexible cell membrane and fluid cytoplasm let the phagocyte change shape so it can wrap around and engulf a pathogen.
   2. Receptors on the membrane detect chemicals from the pathogen, so the phagocyte can move towards the site of infection.
   3. Large numbers of lysosomes in the cytoplasm provide the enzymes needed to digest the engulfed pathogen.
   4. A lobed nucleus makes the cell flexible enough to squeeze through the gaps between the cells of capillary walls, so it can leave the blood and reach pathogens in infected tissue.
5. Many phagocytes die after engulfing large numbers of bacteria, and the pus in an infected cut is largely made of dead phagocytes and the remains of pathogens.

Lymphocytes

1. A lymphocyte is a white blood cell with a large, round nucleus that fills most of the cell and leaves only a thin layer of cytoplasm around it.
2. Lymphocytes defend the body by producing antibodies and antitoxins, which are both proteins.
3. Antibodies bind to antigens, the molecules on the surface of a pathogen, and each antibody has a shape that fits only one type of antigen.
4. Antitoxins bind to the toxins released by some bacteria and stop the toxins damaging body cells.
5. Each feature of a lymphocyte is linked to making these proteins in large amounts.
   1. The large nucleus contains the genes that code for the antibody proteins.
   2. The cytoplasm contains many ribosomes, which are the sites of protein synthesis, so the cell can make antibody molecules quickly.
   3. A well-developed network of membranes inside the cytoplasm packages the antibodies so they can be released from the cell in large numbers.
   4. A lymphocyte that meets its matching antigen can divide rapidly by mitosis, producing many identical lymphocytes that all make the same antibody.
6. Because each lymphocyte makes only one kind of antibody, lymphocytes give a specific defence that targets one pathogen at a time.
7. Lymphocytes work more slowly than phagocytes the first time a pathogen is met, because the right lymphocytes must first multiply before enough antibody is made.

Platelets and blood clotting

1. Platelets are small, disc-shaped fragments of large cells in the bone marrow, and they have no nucleus.
2. Their small size lets huge numbers of them circulate in every blood vessel, so there are always platelets close to any wound.
3. When a blood vessel is cut, platelets stick to the damaged vessel wall and to one another, forming a loose platelet plug over the gap.
4. The platelets and the damaged tissue then release chemicals that set off a chain of reactions in the plasma.
5. These reactions convert the soluble plasma protein fibrinogen into insoluble threads of fibrin.
6. The fibrin threads form a mesh across the wound that traps red blood cells and more platelets, producing a blood clot.
7. At the surface of the skin the clot dries and hardens into a scab, which stays in place while new skin grows underneath.
8. The clot has two defence functions.
   1. It stops blood loss, which prevents the loss of blood volume and the fall in blood pressure that would follow.
   2. It forms a barrier that stops pathogens entering the body through the break in the skin.
9. A person with too few platelets bruises easily and bleeds for longer from small cuts, which shows how important platelets are to sealing wounds quickly.

6.3.9 Non-specific defence systems

Non-specific defences

1. A pathogen can only cause disease once it has entered the body and begun to reproduce in the tissues.
2. The body's first line of protection is a set of non-specific defences that stop pathogens getting in, or kill them at the point of entry.
3. They are called non-specific because they act against all pathogens in the same way, whether the invader is a virus, a bacterium, a fungus or a protist.
4. They are also always present, so they work immediately and do not need the body to have met the pathogen before.
5. The non-specific defences fall into two groups.
   1. Physical barriers block the entry of pathogens, and include the skin, the hairs and mucus of the nose, and the mucus and cilia of the airways.
   2. Chemical defences kill pathogens or stop them growing, and include stomach acid and the enzyme lysozyme in tears and saliva.
6. Every place where the body is open to the outside, such as the nose, mouth, eyes and breaks in the skin, is protected by at least one of these defences.

The skin

1. The skin covers the whole outer surface of the body and is the largest barrier to pathogens.
2. Its outer layer is made of many layers of dead cells packed with a tough protein, so pathogens cannot pass through intact skin and there are no living cells for viruses to infect.
3. These dead cells are constantly worn away and replaced, so any pathogens settled on the surface are shed with them.
4. Glands in the skin secrete an oily substance called sebum, which waterproofs the surface and contains chemicals that slow the growth of microorganisms.
5. Sweat keeps the skin surface slightly acidic and salty, which many bacteria cannot grow in.
6. Harmless microorganisms live naturally on healthy skin, and they compete with pathogens for space and nutrients so that pathogens find it harder to settle.
7. When the skin is cut, the barrier is broken, and a blood clot quickly seals the wound so that pathogens cannot enter through the gap.
8. Burns and large wounds are serious partly because they remove a wide area of this barrier, which is why patients with burns are at high risk of infection.

The nose and airways

1. Every breath draws air containing dust, bacteria, viruses and fungal spores into the body.
2. The nose is the first filter, because the hairs inside the nostrils trap large particles and the mucus lining the nasal cavity traps smaller ones.
3. The trachea and bronchi are lined with two types of cell that work together.
   1. Goblet cells secrete sticky mucus that coats the lining and traps pathogens and dust as air flows past.
   2. Ciliated epithelial cells carry cilia on their surface, which beat in a coordinated wave.
4. The beating cilia sweep the mucus, carrying its trapped pathogens, upwards and away from the lungs towards the back of the throat.
5. The mucus is then swallowed, so the pathogens reach the stomach, where the acid kills most of them.
6. This system keeps the delicate alveoli almost free of pathogens, which matters because the thin walls of the alveoli would be easy for pathogens to cross.
7. Smoking damages this defence, because chemicals in tobacco smoke stop the cilia beating and cause more mucus to be made.
8. Mucus then collects in the airways, and smokers cough to move it, which is why smokers suffer more chest infections such as bronchitis.

Chemical defences

1. Food and drink always carry some microorganisms, and the stomach is the main defence against those that are swallowed.
2. Cells in the stomach lining secrete hydrochloric acid, which gives the stomach contents a pH of about $2$.
3. This acidity denatures the enzymes and other proteins of most pathogens, so they are killed before they reach the intestines.
4. Some pathogens survive the acid, and this is how food poisoning bacteria such as Salmonella can still cause disease when a large number are eaten.
5. Tears, saliva and mucus contain an enzyme called lysozyme.
6. Lysozyme digests the cell walls of bacteria, so the bacterial cells burst and die.
7. Tears wash over the surface of the eye every time you blink, so bacteria landing on the eye are both washed away and attacked by lysozyme.

6.3.10 The immune system

Antigens and the immune system

1. Pathogens that get past the skin, mucus and other barriers enter the tissues and the blood, where the immune system is the next line of defence.
2. The immune system is made up of the white blood cells and the proteins they release, and its job is to find and destroy pathogens inside the body.
3. Phagocytes give the first, non-specific part of this response by engulfing and digesting any pathogen they meet.
4. Lymphocytes give the specific immune response, which targets one particular type of pathogen and destroys it far more effectively.
5. To respond to a pathogen, the immune system must first recognise it as foreign.
6. Every cell has molecules called antigens on its surface, and these are usually proteins with a particular three-dimensional shape.
7. The antigens on your own cells are recognised as self, so lymphocytes do not attack them.
8. The antigens on a pathogen have different shapes, so they are recognised as non-self, and this is what triggers the response.
9. Each type of pathogen carries its own unique antigens, so the measles virus, the chickenpox virus and the bacterium that causes tuberculosis each trigger a different response.

How antibodies destroy pathogens

1. The body contains millions of different lymphocytes, and each one carries receptors of one shape and can make antibodies of only that shape.
2. When a pathogen enters the body, only the lymphocytes whose antibodies are complementary to its antigens can bind to it.
3. The specific immune response then follows a sequence of steps.
   1. The lymphocyte with the matching antibody binds to the antigen and is activated.
   2. The activated lymphocyte divides rapidly by mitosis, producing a clone of many genetically identical lymphocytes.
   3. The cloned lymphocytes release large numbers of antibodies into the blood, all with the same shape.
   4. The antibodies bind to the antigens on the surface of the pathogens.
4. An antibody is a Y-shaped protein with two identical binding sites, one at the tip of each arm.
5. Each binding site has a shape that is complementary to one antigen, so the antibody fits that antigen and no other.
6. Once they have bound, antibodies destroy pathogens in several ways.
   1. Because each antibody has two binding sites, it can attach to two pathogens at once, and this causes agglutination, the clumping of many pathogens together.
   2. Clumped pathogens cannot spread through the body as easily, and a phagocyte can engulf a whole clump at once.
   3. Bound antibodies act as markers that tag the pathogen, so phagocytes recognise and engulf it more quickly.
   4. Antibodies that cover the antigens of a virus stop it attaching to and entering host cells, so it cannot reproduce.
7. The phagocytes then engulf and digest the tagged and clumped pathogens, so the two types of white blood cell work together.

Antitoxins

1. Some bacteria cause the symptoms of disease by releasing toxins, which are poisonous substances that damage body cells.
2. The toxins released by the bacteria that cause tetanus and diphtheria are examples, and these toxins can be fatal even when the number of bacteria is small.
3. Lymphocytes respond by producing antitoxins, which are proteins with a shape complementary to one particular toxin.
4. An antitoxin binds to the toxin and neutralises it, so the toxin can no longer damage cells.
5. Antitoxins deal with the toxin while antibodies and phagocytes deal with the bacteria that are releasing it.

Memory cells and immunity

1. When a lymphocyte is activated and divides, some of the cells in the clone do not release antibodies straight away but become memory cells.
2. Memory cells stay in the blood for many years, sometimes for life, after the infection has been cleared.
3. If the same pathogen enters the body again, the memory cells recognise its antigens immediately.
4. They divide rapidly and produce antibodies much faster and in much larger amounts than the first time.
5. The pathogens are destroyed before they can reproduce enough to cause symptoms, so the person does not become ill.
6. A person who has memory cells for a pathogen in this way has immunity to the disease that it causes.
7. Immunity is specific to one pathogen, so having had chickenpox gives immunity to chickenpox but no protection against measles.

Primary and secondary responses

1. The response to the first exposure to a pathogen is called the primary immune response.
2. It is slow, because only a few lymphocytes have the right antibody shape and they must divide many times before much antibody is made.
3. There is a delay of several days before antibody appears in the blood, and during this time the pathogens reproduce and the person develops symptoms.
4. The concentration of antibody peaks after about one to two weeks and then falls as the pathogen is cleared.
5. The response to a later exposure to the same pathogen is called the secondary immune response.
6. It is faster, because memory cells are already present and start producing antibody within a day or two.
7. It is larger, because there are many more memory cells than there were matching lymphocytes at the start, so the peak concentration of antibody is often ten times higher or more.
8. It lasts longer, so antibody stays in the blood at a high concentration for longer.
9. On a graph of antibody concentration against time, the secondary response therefore appears as a curve that rises sooner, climbs more steeply and reaches a much higher peak than the primary response.

6.3.11 Monoclonal antibodies

What monoclonal antibodies are

1. An antibody binds only to the antigen whose shape is complementary to its binding sites, which makes antibodies extremely precise tools for finding one particular molecule.
2. The antibodies in your blood after an infection come from many different lymphocytes, so they are a mixture of slightly different shapes.
3. Monoclonal antibodies are different because they all come from a single clone of cells, so every antibody molecule is identical and binds to exactly the same antigen.
4. Scientists can choose the antigen, so monoclonal antibodies can be made to bind to a hormone, a protein on a pathogen, a chemical in the blood or a protein found only on cancer cells.
5. Making large amounts of one antibody is difficult, because a lymphocyte that makes the antibody does not divide when it is grown outside the body.
6. The solution is to join the lymphocyte to a cell that does divide, which is the basis of the method used to produce them.

Producing monoclonal antibodies

1. Monoclonal antibodies are produced in a series of steps.
   1. A mouse is injected with the chosen antigen, such as a protein found on a particular pathogen.
   2. The mouse's immune system responds, and its lymphocytes begin to produce antibodies complementary to that antigen.
   3. The lymphocytes are removed from the mouse, usually from its spleen.
   4. The lymphocytes are fused with tumour cells, which are cells that divide over and over without stopping.
   5. Each fused cell is called a hybridoma cell.
   6. The hybridoma cells are separated and tested, and a single hybridoma cell that makes the wanted antibody is selected.
   7. The selected cell is grown in a culture, where it divides repeatedly to produce a clone of identical hybridoma cells.
   8. The clone releases large amounts of one antibody, which is collected from the culture and purified.
2. The hybridoma combines the useful property of each parent cell.
   1. From the lymphocyte it inherits the ability to make one specific antibody.
   2. From the tumour cell it inherits the ability to divide rapidly and indefinitely.
3. Because all the cells in the culture come from one hybridoma cell, all the antibodies they release are identical, which is where the name monoclonal comes from.
4. The culture can be kept going for years, so a steady supply of the same antibody can be produced for tests and treatments.

Pregnancy tests

1. A developing embryo releases a hormone called human chorionic gonadotrophin, or hCG, which passes into the mother's blood and then into her urine.
2. A home pregnancy test uses monoclonal antibodies that are complementary to hCG to detect it in a urine sample.
3. The test stick has three important zones, each containing a different set of monoclonal antibodies.
   1. The reaction zone near the tip holds mobile antibodies that bind to hCG and that carry a coloured dye or a blue bead.
   2. The test line holds antibodies fixed to the strip that also bind to hCG.
   3. The control line holds fixed antibodies that bind to the mobile antibodies themselves, whether or not they are carrying hCG.
4. Urine is placed on the tip of the stick and soaks along the strip, carrying the mobile antibodies with it.
5. If hCG is present, it binds to the mobile antibodies, and the hCG-antibody complexes are then caught by the fixed antibodies at the test line, which turns coloured.
6. If there is no hCG, the mobile antibodies pass the test line without being caught, so the test line stays blank.
7. In both cases the remaining mobile antibodies are caught at the control line, which turns coloured to show that the test has worked.

Detecting disease

1. Monoclonal antibodies are used in hospital laboratories to detect and measure particular molecules in samples of blood.
2. Men with prostate cancer often have raised levels of a protein called prostate-specific antigen, or PSA, in their blood.
3. Monoclonal antibodies complementary to PSA are attached to a dye or a fluorescent marker and mixed with a blood sample.
4. The antibodies bind only to PSA, so the amount of colour or fluorescence shows how much PSA is present.
5. A high PSA level is a signal that the man should have further tests, although PSA can also be raised by other conditions of the prostate.
6. Monoclonal antibodies are also used to locate diseased tissue inside the body.
   1. Antibodies that bind to an antigen found only on cancer cells are attached to a radioactive or fluorescent marker.
   2. The labelled antibodies are injected and travel in the blood until they bind to the cancer cells.
   3. A scanner detects where the marker has built up, which shows the position and size of a tumour.
7. The same approach can detect a pathogen in a blood or tissue sample, or find the position of a blood clot, by choosing an antibody that binds to that pathogen or to a protein in the clot.

Treating disease

1. Monoclonal antibodies can potentially be used to treat cancer by carrying a treatment directly to the cancer cells.
2. A monoclonal antibody that binds to an antigen found only on the surface of cancer cells is made first.
3. A drug, a toxin or a radioactive substance is then attached to the antibody.
4. When the antibody is injected, it binds only to the cancer cells, so the attached substance kills the cancer cells while leaving healthy cells largely unharmed.
5. Some monoclonal antibodies work without any attached substance, by binding to cancer cells and marking them so that the patient's own white blood cells destroy them.
6. Targeting the treatment in this way should cause fewer side effects than treatments such as chemotherapy, which damage healthy dividing cells throughout the body.
7. Monoclonal antibodies also have disadvantages that have limited their use.
   1. They have caused more side effects than was expected when they were first developed, such as fever, vomiting and a fall in blood pressure.
   2. They are expensive to develop and to produce.
   3. Their production uses mice, which some people object to on ethical grounds.

6.3.12 Vaccines and medicines

Vaccines

1. A vaccine contains a harmless form of a pathogen that still carries the pathogen's antigens.
2. The harmless form can be made in several different ways.
   1. Dead or inactivated pathogens, which cannot reproduce at all.
   2. Weakened pathogens, which can reproduce only very slowly and do not cause the disease in a healthy person.
   3. Fragments of the pathogen, such as its surface proteins, which carry the antigens without the rest of the pathogen.
   4. Genetic instructions for one antigen, which body cells use to make that antigen for a short time.
3. Most vaccines are given by injection, although a few are given by mouth or as a nasal spray.
4. Because the antigens have the same shape as those on the live pathogen, the immune system responds to the vaccine exactly as it would to a real infection.
5. The vaccine cannot cause the disease, so the person gains protection without the risk of becoming seriously ill.

How vaccines prevent disease

1. A vaccine is given before the person meets the pathogen, so vaccination is a way of preventing disease rather than treating it.
2. Vaccination works by starting the immune response in advance.
   1. The lymphocytes with antibodies complementary to the vaccine's antigens bind to them, divide and release antibodies.
   2. Some of the cloned lymphocytes become memory cells, which remain in the blood.
   3. If the live pathogen later enters the body, the memory cells recognise its antigens straight away.
   4. They produce the matching antibodies rapidly and in large amounts, in a secondary response.
   5. The pathogens are destroyed before they can cause symptoms, so the vaccinated person does not become ill.
3. The number of memory cells can fall over the years, so some vaccines are followed by a booster dose that raises the number of memory cells again.
4. In the UK the tetanus vaccine is given several times through childhood for this reason.
5. A vaccine protects against one disease only, because the memory cells it produces recognise only the antigens in that vaccine.
6. Some vaccines, such as the flu vaccine, must be changed every year, because the flu virus changes its antigens and last year's memory cells no longer match.

Herd immunity

1. A vaccinated person cannot carry and pass on the pathogen easily, because the pathogen is destroyed soon after it enters their body.
2. When a high proportion of a population is vaccinated, a pathogen rarely finds an unvaccinated person to infect, so it cannot spread.
3. This protects the few people who are not immune, and the effect is called herd immunity.
4. Herd immunity protects people who cannot be vaccinated, such as babies too young for a vaccine, people having cancer treatment and people with a weakened immune system.
5. The proportion needed depends on how easily the disease spreads, and for measles about $95\%$ of the population must be immune.
6. If vaccination rates fall below this level, outbreaks return, as happened with measles in parts of the UK when fewer children received the MMR vaccine.
7. Vaccination on a worldwide scale can eradicate a disease completely, and smallpox was declared eradicated in $1980$ after a global vaccination programme.

Benefits and risks of vaccination

1. The decision to vaccinate every child routinely is made by weighing the benefits against the risks.
2. The benefits are large and are felt by the whole population.
   1. Vaccinated children are protected from diseases such as measles, which can cause brain damage and death.
   2. Epidemics are prevented, and herd immunity protects those who cannot be vaccinated.
   3. Fewer people need hospital care, which reduces the cost to the NHS.
3. The risks are small but real.
   1. Many people have mild side effects, such as a sore arm or a slight fever for a day or two.
   2. A very small number of people have a serious reaction, such as a severe allergic reaction to one of the ingredients.
   3. Vaccination does not guarantee protection, because a small number of people do not produce enough memory cells.
4. Some people choose not to vaccinate their children for personal, religious or ethical reasons, which raises the question of whether individual choice or the protection of others should come first.

Antibiotics

1. Medicines are used to treat a disease once a person is ill, or in some cases to prevent it.
2. Antibiotics are medicines that kill bacteria inside the body or stop them growing and dividing.
3. They work by damaging structures or processes found in bacterial cells but not in human cells, such as the bacterial cell wall, so they harm the bacteria without harming the patient's own cells.
4. Penicillin, the first widely used antibiotic, works by stopping bacteria building their cell walls, so the bacteria burst.
5. Different antibiotics work against different bacteria, so the doctor must choose one that will kill the particular bacterium causing the infection.
6. Antibiotics have no effect on viruses, because viruses have no cell wall and reproduce inside the patient's own cells, where an antibiotic cannot reach them without harming the cell.
7. Some painkillers, such as paracetamol, are also medicines, but they only relieve the symptoms and do not kill the pathogen.
8. The overuse of antibiotics has allowed antibiotic-resistant bacteria to become common, so antibiotics are prescribed only for bacterial infections that need them, and the full course should be completed.

Antivirals

1. Antivirals are medicines used to treat infections caused by viruses.
2. They work by stopping the virus reproducing inside host cells, for example by blocking an enzyme the virus needs to copy itself.
3. Antivirals are difficult to develop, because viruses use the host cell's own machinery, so a drug that stops the virus can easily damage the host cell too.
4. Most antivirals slow down a viral infection rather than cure it, which gives the immune system more time to destroy the virus.
5. People with HIV take a combination of antiviral drugs every day, which keeps the amount of virus in the blood so low that it does not develop into AIDS.
6. Antivirals can also be used against flu in people at high risk, such as elderly people in a care home during an outbreak.
7. Viruses change quickly, so an antiviral that works against one strain can stop working against a new one.

Antiseptics

1. Antiseptics are chemicals applied to the outside of the body, on the skin or on a wound, that kill microorganisms or stop their growth.
2. They are used to prevent infection rather than treat it, by reducing the number of pathogens before they enter the body.
3. Alcohol hand gels used in hospitals and schools, and the solutions used to clean the skin before an injection or an operation, are examples of antiseptics.
4. Antiseptics are too harmful to be swallowed or injected, so they cannot be used to treat an infection that is already inside the body.
5. Disinfectants are similar chemicals used on non-living surfaces such as floors, worktops and surgical instruments, and they are too strong to use on skin.
6. Regular hand washing and the use of antiseptic gels in hospitals have reduced the spread of infections from one patient to another.

6.3.13 Aseptic techniques

Culturing microorganisms

1. Microorganisms are grown, or cultured, in the laboratory so that they can be studied, identified and used to test substances such as antibiotics and antiseptics.
2. They are grown on a culture medium that supplies everything they need to grow.
   1. Carbohydrates, such as glucose, provide a source of energy for respiration.
   2. Proteins or other nitrogen compounds provide the raw material for making new proteins.
   3. Mineral ions and vitamins are needed for healthy growth.
   4. Water is needed for all the chemical reactions inside the cells.
3. The medium can be a liquid called nutrient broth, or a jelly called nutrient agar, which is melted, poured into a Petri dish and left to set.
4. Bacteria reproduce by splitting in two, and in good conditions some bacteria divide as often as once every $20$ minutes.
5. A single bacterium placed on agar divides again and again until a visible colony of millions of identical cells forms on the surface.
6. When a liquid culture is spread evenly across the whole plate, the bacteria grow into a continuous layer called a bacterial lawn.
7. Any culture should contain only the one type of microorganism being studied, and the methods used to keep it that way are called aseptic techniques.

Why aseptic technique is needed

1. Aseptic technique has two separate purposes, and a good answer always gives both.
2. The first purpose is to prevent contamination of the culture by unwanted microorganisms.
   1. Microorganisms are present on hands, benches, equipment and dust in the air, and any that reach the medium will grow alongside the culture.
   2. Unwanted microorganisms compete with the culture for nutrients and space, so the results of the investigation are no longer valid.
3. The second purpose is to protect people from pathogens.
   1. A contaminating microorganism could be a pathogen that grows to large numbers on the plate.
   2. Even a harmless culture could produce a mutated, harmful strain as it divides millions of times.
4. For these reasons school cultures use only harmless bacteria, and every culture is treated as though it could be harmful.

Sterilising equipment and media

1. Before any microorganisms are transferred, every piece of equipment and all of the culture medium must be sterilised so that no living microorganisms are left on or in them.
2. Glassware, culture media and solutions are sterilised in an autoclave.
   1. An autoclave works like a large pressure cooker, heating items with steam at high pressure to about $121{}^{\circ }C$.
   2. Items are usually kept at this temperature for about $15$ minutes.
   3. The high temperature kills all bacteria, fungi and viruses, including the tough spores that some bacteria form, which boiling water at $100{}^{\circ }C$ would not kill.
3. Plastic Petri dishes and pipettes are bought already sterilised, having been treated with radiation in a sealed pack, and they should only be unwrapped just before use.
4. The inoculating loop is sterilised by flaming.
   1. The wire loop is held in the hottest part of a blue Bunsen flame until it glows red hot, which kills any microorganisms on it.
   2. The loop is then held still for a few seconds to cool, because a hot loop would kill the microorganisms it is about to pick up.
5. The neck of a bottle of culture is passed briefly through the flame after its lid is removed and again before the lid is replaced, which kills microorganisms at the opening and creates an upward current of air.
6. Alcohol, such as ethanol, is used to wipe down the bench before and after the work, which kills microorganisms on the surface.
7. A glass spreader is dipped in alcohol and then passed through the flame so the alcohol burns off, which sterilises it without melting it.

Keeping contaminants out

1. Once everything is sterile, the aim is to stop microorganisms from the air and from your body falling onto or into the medium.
2. Work is carried out close to a lit Bunsen burner, because the flame heats the air above it, and the rising current of warm air carries airborne microorganisms upwards and away from the plate.
3. The lid of the Petri dish is lifted only slightly and at an angle, and only for as short a time as possible, so that the lid acts as a shield against falling dust.
4. Lids of bottles are held in the hand rather than put down on the bench, where they would pick up microorganisms.
5. You should not talk, cough or breathe over an open plate, because droplets from the mouth and nose carry bacteria.
6. After inoculation, the lid is secured with two short strips of tape rather than sealed all the way round.
   1. The tape stops the lid being knocked off or lifted, so microorganisms from the air cannot get in and the culture cannot get out.
   2. Leaving gaps lets oxygen in, which stops the growth of harmful anaerobic bacteria that grow without oxygen.
7. The plate is labelled on the base, not the lid, and incubated upside down, so that drops of water condensing on the lid do not fall onto the agar and spread the colonies.
8. In school laboratories plates are incubated at no higher than $25{}^{\circ }C$, because warmer temperatures close to body temperature, $37{}^{\circ }C$, favour the growth of human pathogens.
9. When the work is finished, plates are never opened, and they are sterilised in an autoclave before they are thrown away.

Measuring the effect of antimicrobial substances

1. A bacterial lawn can be used to compare how well different antiseptics or antibiotics kill bacteria.
2. Paper discs soaked in each substance are placed on the lawn before incubation, and the substance spreads out from each disc into the agar.
3. Where the concentration is high enough, the bacteria are killed or cannot grow, leaving a clear ring called a zone of inhibition around the disc.
4. The larger the zone of inhibition, the more effective the substance is at killing or stopping the growth of that bacterium.
5. A zone is roughly circular, so its size is best compared by calculating its area from its radius using the equation $A=\pi r^2$.
6. The radius $r$ is half of the diameter, so the diameter is measured across the widest part of the zone with a ruler and then halved.
7. The same equation can be used to find the area of a single circular colony or of a whole Petri dish.
8. To improve the reliability of the results, each substance is tested on several plates and a mean zone area is calculated.

6.3.14 Discovery and development of new medicines

Discovering new medicines

1. A drug changes the way the body works, and a medicine is a drug that is used to prevent or treat disease or to relieve its symptoms.
2. Many of the first medicines were found in plants, which make chemicals to defend themselves against pathogens and animals.
   1. Digitalis, which slows and strengthens the heartbeat in people with heart failure, comes from foxgloves.
   2. Aspirin, a painkiller, was developed from a chemical found in the bark of willow trees.
3. Other medicines have been found in microorganisms.
   1. In $1928$ Alexander Fleming noticed that a mould called Penicillium had killed the bacteria growing around it on a Petri dish.
   2. The substance released by the mould was the antibiotic penicillin.
   3. Penicillin was not produced in large amounts until the early 1940s, when Howard Florey and Ernst Chain found a way to purify it and test it on patients.
4. Most new medicines are now made, or synthesised, by chemists in the laboratory.
5. Scientists first identify a target, such as a protein that a pathogen needs or a protein that is not working properly in a disease.
6. Computers are used to model the shape of the target and design molecules that might bind to it.
7. Huge libraries of chemicals, containing hundreds of thousands of compounds, are also tested automatically against the target to find any that have the right effect.
8. A compound that looks promising is called a potential new medicine, and it must now be tested thoroughly before it can be given to patients.
9. Most potential medicines fail during testing, and only a very small proportion of the compounds first identified ever reach patients.

Preclinical testing

1. Preclinical testing is carried out in the laboratory before a potential medicine is given to any human.
2. It checks three things about the medicine.
   1. Its toxicity, which is whether it is harmful to cells and to the body.
   2. Its efficacy, which is whether it has the effect it is meant to have.
   3. The dose that is likely to be effective without being harmful.
3. The medicine is first tested on cells and tissues grown in the laboratory.
   1. These tests are quick and cheap, and they show whether the medicine damages living cells.
   2. They cannot show how the medicine affects a whole body, with its many organs working together.
4. It is then tested on live animals, usually mice or rats, and in the UK a second species of animal is normally used as well.
   1. Animal tests show how the medicine is absorbed, carried around the body, broken down and removed.
   2. They show whether it harms any organ, such as the liver or kidneys.
5. Animal testing has limitations and raises ethical questions.
   1. The bodies of animals differ from human bodies, so a medicine that is safe in mice may still harm humans.
   2. Some people believe it is wrong to cause animals harm or suffering to test medicines.
   3. UK law requires animal tests to use as few animals as possible and to reduce any suffering.
6. Only medicines that pass preclinical testing are allowed to move on to testing in humans.

Clinical trials

1. Clinical trials test the potential medicine on human volunteers, and they are carried out in phases, each involving more people.
2. In the first phase the medicine is given to a small number of healthy volunteers, often between $20$ and $100$ people.
   1. It starts at a very low dose, which is then increased slowly.
   2. The aim is to check that the medicine is safe in humans and to find any side effects.
   3. Healthy volunteers are used because the aim is only to test safety, and a person who is already ill might react badly to an untested drug.
3. In the second phase the medicine is given to a small number of patients who have the disease.
   1. This tests whether the medicine works in people with the illness.
   2. Different doses are compared to find the optimum dose, which is the dose that works best with the fewest side effects.
4. In the third phase the medicine is given to a large number of patients, often several thousand, in many different hospitals.
   1. The medicine is compared with a placebo or with the best existing treatment.
   2. The large number of patients means that rare side effects are more likely to be found and that the results are more reliable.
5. A clinical trial can be stopped at any point if the medicine causes serious side effects or clearly does not work.
6. The whole process from discovery to a medicine being available often takes more than ten years and costs a very large amount of money.

Placebos and blind trials

1. People often feel better after taking any treatment simply because they expect it to help, and this is called the placebo effect.
2. To show that a medicine really works, the patients are split at random into two groups.
   1. One group receives the medicine being tested.
   2. The other group, called the control group, receives a placebo, a dummy tablet or injection that looks the same but contains no active drug.
3. If the group taking the medicine improves more than the placebo group, the difference must be caused by the medicine itself.
4. Patients are placed in the groups at random, so each group has a similar mix of ages, sexes and severity of illness.
5. In a blind trial, the patients do not know which group they are in, so their expectations cannot affect the results.
6. In a double-blind trial, neither the patients nor the doctors know who is receiving the medicine and who is receiving the placebo.
   1. This removes bias from the doctors as well, because a doctor who knows which patient has the medicine might treat them differently or judge their improvement more favourably.
   2. The information about who received what is held by a third party and revealed only when the trial ends.
7. It can be unethical to give a placebo to a patient with a serious illness, because it means withholding a treatment that could help them.
8. In these cases the new medicine is compared with the best existing treatment instead of a placebo.

Approval and publication

1. When a trial is finished, the scientists write up their methods and results and send them to a scientific journal.
2. Before it is published, the work goes through peer review, in which other scientists who are experts in the same field check it.
3. Peer review checks that the methods were suitable, that the results support the conclusions, and that no mistakes or false claims have been made.
4. Publishing the results allows other scientists to repeat the work and check that they get the same results.
5. In the UK a medicine can only be sold once the Medicines and Healthcare products Regulatory Agency, the MHRA, has examined all the trial data and granted a licence.
6. Doctors continue to report side effects after the medicine is licensed, because very rare side effects may only appear once millions of people have taken it.

6.3.15 Causes of non-communicable diseases

Non-communicable diseases

1. A non-communicable disease is not caused by a pathogen, so it cannot be passed from one person to another.
2. Most non-communicable diseases develop slowly over many years and last for a long time once they appear.
3. Very few of them have a single cause, because most arise from the interaction of several factors acting on the body at the same time.
4. These factors fall into three groups.
   1. Genetic factors are the alleles a person inherits, which can make them more or less likely to develop a disease.
   2. Lifestyle factors are the choices a person makes, such as their diet, how much exercise they take, whether they smoke and how much alcohol they drink.
   3. Environmental factors are features of a person's surroundings, such as air pollution, harmful chemicals breathed in at work or ultraviolet light from the Sun.
5. Each of these factors is called a risk factor, because it raises the probability of developing a disease without making the disease certain.
6. A person with no obvious risk factors can still develop a non-communicable disease, and a person with several risk factors may never develop one.
7. When risk factors combine, the overall risk usually rises by more than the risk from each factor on its own, because the factors often damage the same organ in different ways.
8. The main non-communicable diseases caused in this way are cardiovascular diseases, many forms of cancer, lung diseases such as bronchitis, liver diseases such as cirrhosis and diseases influenced by nutrition, including type 2 diabetes.

Cardiovascular disease

1. Cardiovascular disease includes coronary heart disease, heart attacks, strokes and high blood pressure.
2. In coronary heart disease, fatty deposits containing cholesterol build up in the inner walls of the coronary arteries, which supply the heart muscle with blood.
3. The deposits narrow the lumen of each artery, so less blood reaches the heart muscle.
4. With less blood, the heart muscle receives less oxygen and glucose, so it cannot carry out enough aerobic respiration to release the energy it needs to contract.
5. If a fatty deposit breaks open, a blood clot can form on it and block the artery completely, and the heart muscle beyond the blockage dies in a heart attack.
6. A clot that blocks an artery supplying the brain causes a stroke.
7. Several risk factors interact to cause cardiovascular disease.
   1. A diet high in saturated fat raises the concentration of cholesterol in the blood, which speeds up the build-up of fatty deposits.
   2. A diet high in salt raises blood pressure, and high blood pressure damages the lining of the arteries so that deposits form more easily.
   3. Smoking damages the lining of the arteries, and the carbon monoxide in the smoke reduces the amount of oxygen the blood can carry, so the heart has to work harder.
   4. The nicotine in tobacco raises the heart rate and blood pressure.
   5. Drinking large amounts of alcohol over many years raises blood pressure.
   6. Lack of exercise and obesity raise blood pressure and blood cholesterol and put extra strain on the heart.
   7. Some people inherit alleles that make their liver produce more cholesterol, so they develop fatty deposits even when they eat a healthy diet.
8. A smoker with high blood pressure and a high-fat diet has a far greater risk than a person with only one of these factors, because each factor adds to the damage in the same arteries.

Cancer

1. Many forms of cancer are caused by the interaction of several factors rather than by a single cause.
2. Smoking is the main risk factor for lung cancer, because tobacco smoke contains chemicals that damage the DNA of the cells lining the airways.
3. Exposure to ultraviolet light from the Sun or from sunbeds increases the risk of skin cancer.
4. Heavy alcohol consumption and obesity both increase the risk of several cancers, including cancers of the mouth, liver, bowel and breast.
5. Some people inherit faulty alleles of genes such as BRCA1 and BRCA2, which greatly increase their risk of breast cancer and ovarian cancer.
6. A person who inherits one of these alleles and also smokes or drinks heavily has a higher risk still, which shows how genetic and lifestyle factors combine.

Bronchitis

1. Bronchitis affects the bronchi, the tubes that carry air into the lungs.
2. The inflamed lining of the bronchi produces extra mucus, and the cilia that normally sweep mucus out of the airways are damaged, so mucus collects in the lungs.
3. The person develops a persistent cough, becomes short of breath and is more likely to get lung infections.
4. When the condition lasts for months or years, it is called chronic bronchitis.
5. The main risk factor is smoking, because the tar and other chemicals in smoke irritate the airways and stop the cilia from beating.
6. Air pollution, including smoke, dust and fumes breathed in at work, also irritates the airways and increases the risk.
7. Inherited differences in how the lungs respond to irritants help to explain why some smokers develop bronchitis while others do not.
8. A smoker who also lives or works in polluted air has a much higher risk than a person exposed to only one of these factors.

Cirrhosis

1. In cirrhosis, healthy liver tissue is gradually replaced by scar tissue.
2. Scar tissue cannot carry out the jobs of the liver, such as breaking down toxins and making important proteins, so the liver slowly fails.
3. The main risk factor is drinking large amounts of alcohol over many years, because liver cells are damaged each time they break down alcohol.
4. Obesity and a diet high in fat and sugar cause fat to build up in the liver, and this can also lead to scarring.
5. Long-term infection with the hepatitis B or hepatitis C virus inflames the liver, so a person who is infected and also drinks heavily is at particularly high risk.
6. Cirrhosis often causes no symptoms until a large part of the liver has been damaged.

Type 2 diabetes

1. Type 2 diabetes is a disease strongly influenced by nutrition.
2. In type 2 diabetes, body cells stop responding properly to the hormone insulin, so blood glucose concentration stays too high after a meal.
3. The strongest risk factor is obesity, especially fat stored around the abdomen.
4. A diet high in sugar and fat, combined with little exercise, leads to weight gain and so increases the risk.
5. The risk also rises with age and is higher in people who have a close relative with the disease, which shows that inherited alleles play a part.
6. Losing weight, eating a balanced diet and taking regular exercise greatly reduce the risk, even for someone with a family history of the disease.

6.3.16 Treatments for cardiovascular disease

Types of treatment

1. Cardiovascular disease can be treated in three main ways: by lifestyle changes, by medicines and by surgery.
2. Most treatments aim to slow the build-up of fatty deposits, to widen or bypass a narrowed artery, or to replace a part of the heart that no longer works.
3. Doctors choose a treatment by weighing its benefits against its risks, its cost and how quickly it works.
4. Many patients receive more than one type of treatment, such as a stent followed by daily medicines and a change of diet.

Lifestyle changes

1. Lifestyle changes are usually the first treatment offered, and they are also advised alongside every other treatment.
2. Eating less saturated fat lowers blood cholesterol, so fatty deposits build up more slowly.
3. Eating less salt lowers blood pressure, which reduces damage to the lining of the arteries.
4. Regular aerobic exercise strengthens the heart muscle, lowers blood pressure and helps with weight loss.
5. Stopping smoking allows the lining of the arteries to recover and removes carbon monoxide from the blood.
6. Drinking less alcohol lowers blood pressure and helps with weight loss.
7. Lifestyle changes have clear benefits.
   1. They are cheap or free, and they have no side effects.
   2. They also reduce the risk of other diseases, such as type 2 diabetes, several cancers and bronchitis.
8. Lifestyle changes also have drawbacks.
   1. They work slowly and cannot clear an artery that is already badly narrowed, so on their own they cannot help a patient in immediate danger.
   2. They only work if the patient keeps to them for the rest of their life, which many people find difficult.

Medicines

1. Statins reduce the amount of cholesterol made by the liver, which lowers blood cholesterol and slows the formation of new fatty deposits.
   1. Statins reduce the risk of heart attacks and strokes, and they are taken as a daily tablet.
   2. They must be taken for life, and some people get side effects such as muscle pain, headaches or, rarely, liver damage.
   3. They take several weeks to have an effect, so they prevent future problems rather than treat an emergency.
2. Anticoagulants, such as warfarin, make the blood less likely to clot, and a daily low dose of aspirin has a similar effect by stopping platelets sticking together.
   1. This reduces the chance of a clot forming on a fatty deposit and blocking a coronary artery or an artery to the brain.
   2. The main risk is excessive bleeding, because cuts and internal injuries take longer to stop bleeding.
3. Antihypertensive drugs lower blood pressure, so the artery walls are damaged less and the heart does not have to work as hard.
   1. Some antihypertensive drugs cause side effects such as dizziness, headaches or swollen ankles.
4. Medicines do not need an operation, they are relatively cheap and they can be started without a stay in hospital.
5. However, medicines control the disease rather than cure it, and most must be taken every day for life.

Stents and bypass surgery

1. A stent is inserted using a thin tube called a catheter, which is passed into an artery in the groin or wrist and guided up to the narrowed coronary artery.
2. A small balloon inside the stent is inflated at the narrowed section, which squashes the fatty deposit against the artery wall and expands the mesh.
3. The balloon is then deflated and removed, leaving the stent in place to hold the artery open.
4. Stents have several benefits.
   1. Blood flow to the heart muscle is restored almost immediately, so a stent can be fitted in an emergency during a heart attack.
   2. The patient usually needs only a local anaesthetic and can often go home within a day or two.
   3. Recovery is much quicker than after open-heart surgery.
5. Stents also have drawbacks.
   1. A blood clot can form on the stent, so the patient must take drugs that reduce clotting afterwards.
   2. The artery can narrow again over time.
   3. There is a small risk of bleeding, infection or damage to the artery during the procedure.
6. In coronary bypass surgery, a length of healthy blood vessel is taken from the patient's leg, arm or chest and attached to the coronary artery above and below the blockage.
7. Blood then flows through the new vessel and bypasses the narrowed section.
8. Bypass surgery is used when several arteries are blocked or when a blockage is too long for a stent.
9. It can relieve chest pain and improve blood flow to the heart muscle for many years.
10. However, it is major surgery under a general anaesthetic, with risks of infection, blood loss and stroke, and recovery takes several weeks.

Replacing heart valves

1. A faulty heart valve may not open fully or may not close properly, so blood flows backwards and the heart has to work harder.
2. A damaged valve can be replaced with a mechanical valve made of metal or plastic, or with a biological valve taken from a pig, a cow or a human donor.
3. Mechanical valves last for many years, but blood can clot on them, so the patient must take anticoagulants for the rest of their life.
4. Biological valves do not need lifelong anticoagulants, but they wear out and may need replacing after $10$ to $20$ years.
5. Both types involve heart surgery, with the risks of infection and blood loss that any major operation carries.

Heart transplants and artificial hearts

1. A heart transplant is used when the heart is so badly damaged that it can no longer pump enough blood around the body, a condition called heart failure.
2. The donor heart usually comes from a person who has died, and its tissue type must match the patient's as closely as possible.
3. The patient's immune system recognises the antigens on the donor cells as foreign, and lymphocytes may attack and destroy the new heart in a process called rejection.
4. To prevent rejection, the patient must take immunosuppressant drugs for the rest of their life.
5. These drugs weaken the whole immune system, so the patient is more likely to catch serious infections.
6. There are far fewer donor hearts than patients who need them, so many people wait a long time for a transplant.
7. An artificial heart is a mechanical pump that can take over the pumping of blood while a patient waits for a donor heart.
8. Artificial hearts are made from materials that do not cause rejection, but blood can clot on them, they carry a risk of infection and the patient's movement is limited by the power supply.
9. Artificial hearts are not yet a permanent replacement for most patients.

6.3.17 Lifestyle factors and non-communicable diseases

Measuring incidence

1. The incidence of a disease is the number of new cases that appear in a population over a set time, usually one year.
2. Because populations differ in size, incidence is normally given as a rate, such as the number of new cases per $100000$ people per year.
3. The incidence rate is calculated using $$incidence\; rate=\frac{number\; of\; new\; cases}{population\; size}\times 100000$$
4. Using a rate allows a small town, a whole country and the whole world to be compared fairly.
5. Incidence data is collected from hospital and GP records and from large health surveys.
6. It is impossible to study everyone, so scientists collect data from a sample of people and use it to draw conclusions about the whole population.
7. For those conclusions to be valid, the sample must be representative, containing the same mix of ages, sexes, incomes and backgrounds as the population.
8. The sample must also be large, because results from a small sample are more likely to be affected by chance.
9. People should be chosen at random, so that the researcher cannot pick people who are likely to give a particular result.
10. Incidence in separate groups, such as different countries or age groups, is shown on a bar chart.
11. When a continuous variable such as alcohol intake is grouped into classes, the data is recorded in a frequency table and shown on a histogram.

Lifestyle factors

1. The four lifestyle factors with the greatest effect on the incidence of non-communicable diseases are smoking, diet, alcohol and exercise.
2. Smoking increases the incidence of lung cancer, several other cancers, bronchitis and cardiovascular disease.
3. A diet high in saturated fat, salt and sugar, or one that provides more energy than the body uses, increases the incidence of cardiovascular disease, obesity and type 2 diabetes.
4. A diet low in fruit, vegetables and fibre is linked to a higher incidence of bowel cancer.
5. Regularly drinking more alcohol than the recommended limit increases the incidence of cirrhosis, several cancers and high blood pressure.
6. In the UK, adults are advised to drink no more than $14$ units of alcohol a week.
7. Taking little exercise increases the incidence of cardiovascular disease, obesity and type 2 diabetes, while regular exercise reduces it.
8. Many people have more than one of these risk factors, so a change in one factor across a population can change the incidence of several diseases at once.

Local, national and global patterns

1. At a local level, incidence can differ greatly between neighbouring areas of the same town or city.
   1. Areas with more deprivation usually have higher rates of smoking and obesity, and so a higher incidence of lung cancer, heart disease and type 2 diabetes.
   2. Local differences also reflect how easy it is to buy healthy food, find safe places to exercise and see a doctor.
2. At a national level, incidence changes over time as the lifestyle of the whole population changes.
   1. In the UK, the proportion of adults who smoke has fallen steadily since the 1970s, and the incidence of lung cancer in men has fallen as a result.
   2. The fall in lung cancer came many years after the fall in smoking, because cancers take a long time to develop.
   3. Over the same period, the proportion of adults who are obese has risen, and the number of people with type 2 diabetes has increased sharply.
   4. National laws, such as banning smoking in enclosed public places, can be followed by falls in the incidence of smoking-related diseases.
3. At a global level, non-communicable diseases cause around three quarters of all deaths.
   1. Incidence has been highest in high-income countries, where diets are rich in fat and sugar and many jobs involve little physical activity.
   2. In many low- and middle-income countries, incidence is now rising quickly as diets change, car use increases and smoking becomes more common.
   3. Comparing countries helps scientists to identify which lifestyle factors matter most, because countries differ in their diet, smoking and drinking habits.

Correlation and cause

1. Data on a lifestyle factor and a disease is often plotted on a scatter diagram, with the lifestyle factor on the $x$-axis and the incidence of the disease on the $y$-axis.
2. If the points slope upwards, there is a positive correlation, meaning the disease is more common where the factor is higher.
3. If the points slope downwards, there is a negative correlation, such as the incidence of heart disease being lower in groups who take more exercise.
4. If the points show no pattern, there is no correlation.
5. A correlation on its own does not prove that the factor causes the disease.
   1. The link may be due to chance, especially when the sample is small.
   2. A third factor may affect both variables, for example older people may exercise less and also be more likely to have heart disease simply because of their age.
6. Scientists accept a causal link when several kinds of evidence agree.
   1. The same correlation is found repeatedly in large, representative samples from different countries.
   2. There is a plausible mechanism that explains how the factor affects the body, such as chemicals in tobacco smoke damaging the DNA of lung cells.
   3. The risk increases as exposure increases, so heavy smokers have a greater risk than light smokers.
   4. Reducing the factor reduces the incidence, as shown by the falling risk of lung cancer in people who stop smoking.

6.3.18 Cancer

Controlled cell division

1. In a healthy body, cells divide by mitosis only when new cells are needed for growth or to repair damaged tissue.
2. The timing of each division is controlled by genes in the nucleus of the cell.
3. Some of these genes make a cell divide when the body needs more cells, while others stop division once enough cells have been made.
4. Cells that are too badly damaged to work properly are normally made to die, so they cannot keep dividing.
5. This control keeps each tissue at the right size and makes sure old or damaged cells are replaced at the same rate as they are lost.

What cancer is

1. Cancer begins when changes in a cell's DNA remove the normal control over when that cell divides.
2. These changes are mutations in the genes that control cell division.
3. A single mutation is rarely enough, and cancer usually develops only after several mutations have built up in the same cell over many years.
4. This is one reason why the risk of most cancers increases with age.
5. The mutated cell divides again and again, and every daughter cell inherits the same mutations, so the abnormal cells keep multiplying.
6. The cancer cells do not respond to the signals that would normally stop division, so they form a growing lump of cells called a tumour.
7. The tumour takes nutrients and space from the healthy cells around it, so the tissue can no longer work normally.
8. Most mutations that cause cancer happen in body cells during a person's life, so most cancers are not inherited.
9. Some people do inherit alleles that make these mutations more likely to lead to cancer, which increases their risk without making cancer certain.

Benign and malignant tumours

1. Tumours are described as benign or malignant, depending on whether their cells can spread.
2. A benign tumour grows in one place, is usually surrounded by a membrane, and does not invade the tissues around it.
3. Benign tumours are not cancer, but they can still be harmful if they press on an organ, such as a benign tumour in the skull pressing on the brain.
4. A benign tumour can often be removed completely by surgery, and it usually does not grow back.
5. A malignant tumour is a cancer, because its cells invade the healthy tissue around it and destroy it.
6. Cells can break away from a malignant tumour and enter the blood or the lymph.
7. These cells are carried to other parts of the body, where they settle and divide to form secondary tumours.
8. The spread of cancer cells in this way is called metastasis.
9. The first tumour to form is the primary tumour, and a cancer is named after the organ where the primary tumour began, even when secondary tumours are found elsewhere.
10. Metastasis makes cancer much harder to treat, because there may be many tumours in different organs.

Causes of the mutations

1. Anything that increases the chance of the mutations that lead to cancer is called a carcinogen.
2. Radiation, including ultraviolet light from the Sun and sunbeds and X-rays, can damage DNA directly.
3. Many chemicals are carcinogens, including dozens of the substances in tobacco smoke and the fibres of asbestos.
4. Some viruses increase the risk of cancer, such as the human papillomavirus, which can cause cervical cancer.
5. Lifestyle factors change how much a person is exposed to carcinogens, which is why smoking, heavy drinking and sunbathing all raise the risk of cancer.

6.3.19 Stem cells in medicine

Stem cells as a treatment

1. A stem cell can divide many times and then differentiate into specialised cells, so it can be used to produce new cells to replace ones that have been damaged or lost.
2. Many diseases and injuries destroy cells that the body cannot replace on its own, such as nerve cells in the spinal cord or the insulin-secreting cells of the pancreas.
3. Stem cells can be grown in the laboratory and treated with chemicals that switch on the genes needed for a particular cell type, so that they differentiate into the cells the patient is missing.
4. The new cells are then placed into the patient's body in a transplant.
5. In the future, stem cells could also be used to grow whole tissues or organs for transplant, which would reduce the shortage of donor organs.
6. Tissues grown from stem cells can also be used to test new drugs, so fewer tests need to be carried out on animals and people.

Uses in medicine

1. Some stem cell treatments are already in routine use.
   1. In a bone marrow transplant, stem cells from a donor's bone marrow are given to a patient with leukaemia, a cancer of the blood, after the patient's own diseased bone marrow has been destroyed.
   2. The donor stem cells divide and differentiate to produce healthy red blood cells, white blood cells and platelets.
   3. Sheets of skin grown from stem cells are used to cover severe burns.
2. Other stem cell treatments are being tested for conditions that cannot yet be cured.
   1. Insulin-secreting cells made from stem cells could treat type 1 diabetes, so the patient would no longer need insulin injections.
   2. New nerve cells could repair damage to the spinal cord and help people with paralysis.
   3. Replacement brain cells could treat Parkinson's disease, in which a group of brain cells that control movement die.
   4. Light-sensitive cells could replace damaged cells in the retina and restore some sight to people with certain types of blindness.

Tissue transplantation and rejection

1. Every cell carries antigens on its surface, and the pattern of these antigens differs from one person to another.
2. When cells from a donor are transplanted, the patient's lymphocytes can recognise the donor's antigens as foreign.
3. The lymphocytes then attack and destroy the transplanted cells, and this is called rejection.
4. To reduce the risk of rejection, doctors choose a donor whose tissue type is as close as possible to the patient's, often a brother or sister.
5. The patient is usually also given immunosuppressant drugs, which reduce the activity of the immune system.
6. Immunosuppressant drugs leave the patient more likely to suffer serious infections, and they may have to be taken for many years.
7. Rejection can be avoided if the stem cells come from the patient's own body, because the cells carry the patient's own antigens.
   1. Adult stem cells can sometimes be collected from the patient's own bone marrow, stored and returned after treatment.
   2. Therapeutic cloning would produce an embryo with the same genes as the patient, so the embryonic stem cells taken from it would not be rejected.
8. A drawback of using a patient's own cells to treat a genetic disorder is that those cells carry the same faulty alleles that caused the disease.

Risks of stem cell treatments

1. Stem cells divide rapidly, and if their division is not controlled after the transplant they could form a tumour and lead to cancer.
2. Stem cells grown in a laboratory could become contaminated with a virus, which would be transferred to the patient and cause an infection.
3. The transplanted cells may not differentiate into the right cell type, or they may not work properly once inside the patient.
4. Many stem cell treatments are still at the research stage, so their long-term effects are not yet known.
5. The treatments are expensive to develop and carry out, so they may not be available to every patient who could benefit.

Ethical issues

1. Collecting embryonic stem cells destroys the embryo, and some people believe that an embryo has the same right to life as a person.
2. Other people argue that an embryo a few days old is a small ball of cells with no nervous system, so it cannot feel pain and is not yet a person.
3. Most embryos used for research are spare embryos left over from IVF treatment, which would otherwise be thrown away.
4. Some people are concerned that therapeutic cloning could lead to attempts to clone whole humans.
5. In the UK, research on human embryos is allowed only under licence, and an embryo may not be kept beyond $14$ days of development.
6. Using adult stem cells avoids destroying embryos, but they can differentiate into only a limited range of cell types, so they cannot be used to treat as many conditions.

6.3.20 Gene technology in medicine

Gene technology in medicine

1. Gene technology in medicine is used in two main ways.
   1. Genetic engineering of microorganisms inserts human genes into bacteria or yeast so that they make human proteins that can be used as medicines.
   2. Gene therapy inserts working alleles into a patient's own cells to treat a genetic disorder.
2. Both uses rely on cutting out a gene and carrying it into another cell using a vector.
3. Each use brings benefits, but each also raises practical difficulties and ethical questions that have to be weighed up.

Medicines made by GM bacteria

1. The human gene for a useful protein, such as insulin, is cut out of human DNA and inserted into a plasmid, which acts as the vector.
2. The plasmid is taken up by bacteria, which become genetically modified.
3. The GM bacteria are grown in large fermenters, where they divide rapidly and every cell uses the human gene to make the human protein.
4. The protein is then extracted from the fermenter and purified so that it can be used as a medicine.
5. Other medicines made in this way include human growth hormone, used to treat children who do not grow normally, and the clotting factors needed by people with haemophilia.
6. Making medicines in GM bacteria has several benefits.
   1. Large quantities of the protein can be made quickly and cheaply, because bacteria reproduce so rapidly.
   2. The protein is identical to the human version, so it is less likely to cause an allergic reaction than insulin extracted from pigs or cows.
   3. The supply does not depend on animals being slaughtered, which some people object to for ethical or religious reasons.
   4. The products are free of human viruses, unlike some clotting factors that were once extracted from donated human blood.
7. There are also drawbacks.
   1. Building fermenters and purifying the product is expensive, so some of these medicines are still costly.
   2. The GM bacteria must be contained carefully, because some people are concerned about the effects if they escaped into the environment.

Gene therapy

1. Many genetic disorders, such as cystic fibrosis, are caused by a faulty allele that stops a cell making a working protein.
2. In gene therapy, a working copy of the allele is inserted into the patient's cells so that the cells can make the missing protein.
3. The working allele is carried into the cells by a vector, usually a virus that has been modified so that it cannot cause disease.
   1. Tiny spheres of lipid called liposomes can also be used, and these can be breathed into the lungs.
4. In somatic gene therapy, only body cells are changed, such as the cells lining the airways of a person with cystic fibrosis.
   1. The change is not passed on to the patient's children.
   2. Body cells are replaced over time, so the treatment may have to be repeated.
5. In germline gene therapy, the allele would be inserted into gametes or an early embryo, so every cell of the person would carry it and it would be passed on to their descendants.
6. Germline gene therapy in humans is not allowed in the UK.
7. Somatic gene therapy has already been used to treat a rare inherited condition in which children are born with almost no working immune system, and some inherited forms of blindness.

Practical considerations

1. It is difficult to get the allele into enough of the right cells, because a vector cannot reach every cell in an organ.
2. The allele may work for only a short time, especially in cells that are regularly replaced, so the treatment has to be repeated.
3. The patient's immune system may recognise a viral vector as foreign and attack it, which can cause inflammation and make repeat treatments less effective.
4. The inserted allele may enter the DNA in the wrong place and disrupt another gene.
5. In a few early trials, this caused some patients to develop leukaemia.
6. Gene therapy works best for disorders caused by a single gene, while most common diseases are influenced by many genes and by the environment.
7. Gene therapies are extremely expensive to develop, and a single treatment can cost hundreds of thousands of pounds.

Ethical considerations

1. Many people support somatic gene therapy, because it treats a patient who has given consent and affects only that person.
2. Germline gene therapy raises greater concern, because it changes future generations who cannot give consent.
3. Some people fear the same technology could be used to choose characteristics that have nothing to do with health, such as height or eye colour, producing so-called designer babies.
4. There is debate about who should decide which conditions are serious enough to be treated.
5. The high cost raises questions of fairness, because treatments may be available only in wealthy countries or to people who can pay.
6. Some people have religious or moral objections to changing human genes at all.
7. Others argue that it would be wrong not to use a technology that could prevent serious suffering.

6.3.21 The human genome and medicine

Reading the human genome

1. The human genome is the complete set of genetic material in a human cell.
2. The Human Genome Project worked out the order of the bases in human DNA and was declared complete in $2003$.
3. Scientists from several countries, including a large team in the UK, shared the work and made the results freely available to researchers everywhere.
4. The project found that the human genome contains around $20000$ genes that code for proteins.
5. Since then, reading a genome has become much faster and cheaper, so a person's whole genome can now be sequenced in a few days.
6. Comparing the genomes of many people shows which alleles are more common in people who have a particular disease.
7. This allows scientists to link particular alleles to an increased risk of disease, and to find out how different alleles affect the way the body responds to drugs.
8. In England, the 100,000 Genomes Project sequenced the genomes of NHS patients with rare diseases and cancers to find the genetic causes of their conditions.

Predicting the likelihood of disease

1. Genetic testing analyses a person's DNA to see whether they carry alleles linked to a disease.
2. For a disorder caused by a single faulty allele, such as cystic fibrosis or Huntington's disease, a test can show whether a person has the disorder or carries the allele.
3. For most common diseases, such as heart disease, type 2 diabetes and many cancers, a test can show only an increased risk, because these diseases also depend on many other genes and on lifestyle.
4. For example, women who carry a faulty BRCA1 or BRCA2 allele have a much higher chance of developing breast cancer or ovarian cancer during their lives.
5. Knowing about an increased risk allows a person to act early.
   1. They can have more frequent screening, such as regular scans, so that a disease is found and treated at an early stage.
   2. They can make lifestyle changes, such as stopping smoking or losing weight, that lower their overall risk.
   3. Some women with a faulty BRCA1 allele choose surgery to remove their breasts or ovaries before cancer can develop.
6. Couples who carry a faulty allele can find out the chance that their children will inherit a genetic disorder.

Drugs targeted to the genome

1. People respond differently to the same drug, partly because they carry different alleles.
2. Some alleles code for liver enzymes that break down drugs faster or more slowly than usual.
   1. A person who breaks a drug down quickly may need a higher dose for it to work.
   2. A person who breaks a drug down slowly may suffer harmful side effects from a normal dose.
3. Testing a patient's genome before treatment lets a doctor choose the drug and dose most likely to work for them with the fewest side effects.
4. This approach is called personalised medicine.
5. Cancer cells carry their own mutations, so reading the genome of a tumour shows which drug is most likely to attack it.
   1. Some breast cancers have cells with extra copies of a gene called HER2, and a drug that targets the protein made by this gene works only on these cancers.
6. Knowing which genes are involved in a disease also helps scientists design new drugs that act on the proteins those genes produce.

Problems and concerns

1. A genetic test for a common disease gives a probability rather than a certainty, so a person told they have a high risk may never develop the disease, while a person told they have a low risk still might.
2. Learning about a high risk of a disease that cannot be prevented or cured, such as Huntington's disease, can cause great anxiety.
3. Genetic information about one person also reveals information about their relatives, who may not want to know it.
4. There are concerns that insurance companies or employers could treat people unfairly if they had access to their genetic information.
5. Genome data must be stored securely, because it is personal and cannot be changed if it is leaked.
6. Genetic testing and targeted drugs are expensive, so they may not be available to everyone who could benefit.
7. The effects of many alleles are not yet understood, so some test results are difficult to interpret.