Biology and Human Welfare

1Disease, pathogen and vector

Health is not merely the absence of disease; it is a state of complete physical, mental and social well-being, and genetic defects, infections, the way you live and the place you live in all move it. When the cause is an organism, two words have to be kept apart. The pathogen is the organism that causes the disease. A vector is the organism that carries the pathogen from one host to another and is usually untroubled by it — the mosquito is the vector, Plasmodium is the pathogen.

The route matters more than the name, because the route is what prevention attacks. Typhoid and amoebiasis travel in contaminated food and water and are stopped by sanitation; the common cold, pneumonia and tuberculosis travel in droplets and are stopped by distance and hygiene; malaria, dengue and filariasis need an insect vector and are stopped by draining the water it breeds in. Ringworm, the one fungal entry in the list, spreads by contact with towels, combs and soil.

Figure. Pathogen table collapsed by transmission mode — air, water/food, vector, contact — so the exam mapping is spatial without inventing organism cartoons.

2The malaria cycle, and why it needs two hosts

Plasmodium cannot finish a generation without both a human and a mosquito, which is why either half of the cycle can be attacked to stop the disease. Several species cause malaria: P. vivax and P. falciparum are the two to know, and it is P. falciparum that causes malignant malaria, the most serious form and the one that can be fatal. Sporozoites enter the blood with the bite of an infected female Anopheles and multiply first in the liver cells. They then enter the red blood cells and burst them, and the rupture releases a toxic substance, haemozoin. It is that release, not the parasite itself, that produces the chill and high fever recurring every three to four days.

Only the female bites, because she needs a blood meal for her eggs; the male feeds on nectar and plant juices and transmits nothing. The parasite's sexual phase happens in the mosquito, not in you: gametocytes taken up with a blood meal fuse in her gut, and the zygote develops into sporozoites that move to her salivary glands, ready for the next bite.

Figure. Both halves are compulsory. The parasite multiplies asexually in you and reproduces sexually in the mosquito, so it cannot complete a generation in either host alone — which is why draining the water she breeds in breaks the cycle as surely as treating the patient does.

One turn of the cycle

1. The biteAn infected female Anopheles injects sporozoites along with her saliva.
2. In the liverThe sporozoites multiply inside liver cells. Nothing is felt yet, which is why symptoms lag days behind the bite.
3. In the red cellsThe parasites enter and rupture the red blood cells, releasing haemozoin: chill, then high fever.
4. Back to the mosquitoGametocytes are taken up in a later blood meal, fuse in her gut, and become sporozoites again.

3Two layers of defence: innate and acquired

Innate immunity is what you were born with. It is non-specific — it does not care which pathogen it is facing — it acts at once, and it never improves with use. Acquired immunity is the opposite on all three counts: it is specific to one pathogen, it is slow the first time it is asked, and it remembers.

Acquired immunity then splits by which lymphocyte does the work. B cells secrete antibodies into the blood and lymph, and because body fluids were once called humours, that arm is humoral immunity. T cells secrete no antibody; they act on the offending cell themselves, which is cell-mediated immunity, and it is the arm that rejects a transplanted organ. Both kinds of lymphocyte come from bone-marrow stem cells, but only T cells mature in the thymus.

Figure. The first fork is the one to get right: innate is non-specific, immediate and memoryless, acquired is specific, slow the first time and remembered. The second fork under acquired is only a question of who does the work — B cells send antibodies out into the fluids, T cells go to the offending cell themselves.

The four innate barriers

1. PhysicalSkin, and the mucus lining the respiratory, gastrointestinal and urogenital tracts, block or trap what tries to get in.
2. PhysiologicalAcid in the stomach, saliva in the mouth and tears in the eyes destroy much of what gets past.
3. CellularNeutrophils, monocytes, macrophages and natural killer cells engulf or kill invaders in blood and tissue.
4. CytokineA virus-infected cell secretes interferons, which protect the uninfected cells around it.

4The antibody: four chains, two arms

Every antibody is built from one repeating unit of four polypeptide chains — two identical long heavy chains and two identical short light chains — which is why the unit is written H₂L₂. Disulphide bonds hold them in a Y. The two tips of the Y are the antigen-binding sites, so a single monomer grips two copies of the same antigen at once, and the stem is the part that phagocytes and complement take hold of.

The tips vary from antibody to antibody and the stem does not, and that is the whole design: one constant handle under an endlessly variable grip. The constant part of the heavy chains is also what sorts antibodies into five classes — IgG, IgA, IgM, IgE and IgD — so the same specificity can be issued with different equipment depending on where the antibody has to work.

Figure. Four chains, two of each, held in a Y by disulphide bonds — one is drawn between the heavy chains at the hinge, and further bonds tie each light chain to the heavy chain beside it. The two tips are identical, so one molecule grips two copies of the same antigen. Vary the tips and you have a new specificity; vary the stem and you have a new class.

5Memory: the primary and secondary responses

Meet an antigen for the first time and the reply is slow and small: the few B cells whose receptor happens to fit must be found and multiplied first, and the antibody level that results is low. Meet the same antigen again and the reply is faster, larger and longer-lasting, because the first encounter left behind memory B and T cells that recognise it immediately. That single difference is the whole basis of vaccination.

A vaccine is a preparation of antigen — a killed or weakened pathogen, or merely its proteins — that provokes a primary response without the disease, so that the real infection meets a system already primed. That is active immunity: you made the antibodies, it took time, and it lasts. An antiserum is the opposite trade, preformed antibodies injected ready-made, as in antivenom or an anti-tetanus injection. It works within minutes, which is why it is what you give after a snakebite, and it is gone in weeks, because no memory cell was ever made.

Nature makes the same trade. The foetus receives IgG across the placenta and the newborn receives IgA in colostrum: immediate protection, borrowed rather than earned, and temporary.

Figure. Each curve is drawn from the moment of its own exposure, so the two differences can be read straight off: the secondary response leaves the baseline sooner and climbs much higher. Neither axis carries numbers, and that is deliberate — the shape is the content, while the size of the jump depends on the antigen, the dose and the person.

Why the second time is different

1. First exposureThe rare B cell whose receptor fits the antigen has to be found and cloned. That search is the lag.
2. Plasma cellsThe clones become plasma cells and pour out antibody; the titre climbs slowly to a modest peak.
3. Memory keptSome of the clone becomes long-lived memory cells instead of dying away with the response.
4. Second exposureThe memory pool is already large and already specific, so antibody appears sooner and reaches far higher.

6HIV, and the cell it destroys

HIV is a retrovirus: it carries its genome as RNA and brings its own reverse transcriptase to copy that RNA into DNA. The DNA copy is then inserted into the host's own chromosome, where it can sit indefinitely. That is why the infection is lifelong, and why the gap between infection and the appearance of AIDS can run to years.

The cell it destroys is the helper T lymphocyte, and that choice is what makes the disease so severe. Helper T cells are the switch that turns on both arms of acquired immunity, so losing them disables antibody production and cell-mediated defence together. AIDS is therefore not one illness but a collapse of defence, and the patient dies of infections a working immune system would have shrugged off. Infection is detected by ELISA, and antiretroviral drugs lengthen life without clearing the virus.

Figure. Two consequences follow from one step. Because the viral DNA is written into the host chromosome, the infection is permanent and can stay quiet for years. Because the cell it is written into is the helper T cell, every round of virus costs the body the one cell that would have organised the reply.

Inside the cell

1. EntryHIV enters a macrophage or a helper T cell; its RNA and its reverse transcriptase go in with it.
2. RNA into DNAReverse transcriptase copies the viral RNA into DNA — the step that gives retroviruses their name.
3. IntegrationThe viral DNA is inserted into the host chromosome and directs the cell to build new virus.
4. CollapseReleased virions infect more helper T cells, and as those cells are lost both arms of acquired immunity fail.

7Cancer: the cell that will not stop dividing

A normal cell divides only when it is told to and stops when it is pressed against its neighbours — that restraint is called contact inhibition, and cancer cells appear to have lost it. The control of growth and differentiation breaks down, division carries on when it should have stopped, and the mass of cells that piles up is a tumour — your own tissue, not an infection.

Tumours come in two kinds, and the difference is the whole prognosis. A benign tumour stays where it arose and does little damage. A malignant tumour is a mass of actively proliferating neoplastic cells that grows into the tissue around it, damaging it and starving it of nutrients. Cells then break away, travel in the blood and start a fresh tumour far off: that is metastasis, the most feared property of a malignant tumour.

What transforms a normal cell is a carcinogen, and they come in three kinds: physical (ionising X-rays and gamma rays, non-ionising ultraviolet), chemical (tobacco smoke, a major cause of lung cancer) and biological (oncogenic viruses, which carry genes of their own called viral oncogenes). But not every route begins outside the cell. Normal cells already carry genes whose ordinary job is to drive division — the proto-oncogenes, also written as cellular oncogenes or c-onc — and activating one at the wrong moment is enough. A proto-oncogene is not an intruder; it is a gene of your own switched on at the wrong time.

Cancer is found by biopsy, by blood and bone-marrow counts in the leukaemias and by CT or MRI for tumours deep inside, and treated by surgery, radiotherapy and chemotherapy together, with immunotherapy added: tumour cells can escape the immune system's notice, so biological response modifiers such as α-interferon are given to rouse it.

Figure. A benign tumour stops at the second box: its cells have escaped the normal restraint on division, but they stay where they formed. Everything after that box is what malignant adds. Only the last arrow is metastasis — growing into the tissue next door is invasion, and a tumour can do that without ever seeding a second one.

8Microbes at work: from curd to biogas

Most microbes never make anyone ill, and a great many of them are put deliberately to work. Lactobacillus curdles milk and leaves it richer in vitamin B₁₂ than it started; the yeast Saccharomyces cerevisiae ferments sugar to carbon dioxide, which raises dough, and to ethanol, which makes wine and beer; Aspergillus niger yields citric acid; and Penicillium notatum gave Alexander Fleming the first antibiotic, penicillin.

Sewage treatment does the same thing on the scale of a city. Primary treatment is purely physical — filtration and sedimentation, which take out grit and floating solids and leave a primary sludge. Secondary treatment is biological: the effluent is agitated with air in an aeration tank, aerobic bacteria grow into flocs, and as they consume the organic matter the BOD of the water falls sharply. The water is then settled again, and the sludge that comes out of that tank is fed to an anaerobic digester, where a quite different set of bacteria turns it into biogas.

Figure. Primary treatment is physical, secondary treatment is biological, and the flocs in the aeration tank are the treatment. BOD measures how much organic matter is left for bacteria to oxidise, so watching it fall is watching the sewage being eaten. A little of the settled sludge goes back to the aeration tank as inoculum; the rest goes to the digester, where anaerobes turn it into biogas.

9Raising the yield: breeding, biofortification, tissue culture

Plant breeding is the deliberate manufacture of a better variety. Collect the variability available, evaluate and select the parents, cross the two that carry the traits you want, then select and test the superior recombinants over several generations before the line is released as a cultivar. It is slow, and it can only recombine traits that already exist somewhere in the crop or its relatives.

Biofortification is that same machinery aimed at nutrition rather than at yield: breeding crops for higher protein, vitamin or mineral content, which reaches far more people than any supplement programme. Tissue culture is a different lever altogether. A single explant, grown on a sterile nutrient medium, forms an unorganised mass called a callus, and growth regulators then induce the callus to form whole plantlets. Because the callus divides by mitosis, the plantlets are somaclones — genetically identical to each other and to the parent — so one prize plant can be turned into thousands, and a virus-free plant obtained from the apical meristem stays virus-free through every copy.

The animal side runs on the same principle of multiplying a good genotype: artificial insemination carries one superior bull's semen to herds it will never visit, and multiple ovulation embryo transfer multiplies the calves a single superior cow can yield in a season.

Figure. A living plant cell with its nucleus intact is totipotent — it carries the whole genome and can be persuaded to rebuild the entire plant. That is why one small explant becomes thousands of plants, and why they are all copies: the callus divides by mitosis, so no new combination of genes is ever made. Take the explant from the apical meristem and the copies are virus-free as well.

From explant to plantlet

1. ExplantA piece of the plant — a bud, a leaf, a scrap of meristem — is cut out under sterile conditions.
2. CallusOn a nutrient medium its cells divide into an unorganised mass, the callus.
3. PlantletsGrowth regulators in the medium make the callus differentiate into shoots and roots.
4. SomaclonesThe plantlets go to soil. Every one of them is genetically identical to the parent.