Germs, Vaccines and Antibiotics

In the 1840s, the big general hospital in Vienna had two maternity clinics. Year after year, a much larger share of mothers died of childbed fever in the First Clinic than in the Second.

Childbed fever is a serious infection that can follow giving birth. Women went to one clinic or the other depending on the day of the week. The First Clinic trained doctors and medical students, who often worked with bodies in autopsies. The Second Clinic trained midwives. What could make the difference, and how would you test your idea?

Explore: watch an immune response and a bacterial population

The simulation has two panels, both in relative units. In the first, you choose whether a person gets a vaccine, then expose them to a pathogen once and later a second time, and watch the antibody level rise and fall. In the second, you start an antibiotic course on a population of bacteria that includes a few resistant cells, then choose to stop the course early or finish it.

Everything below is “in this sketch”: relative units, not to scale, and a model of the logic. It is not medical advice.

1. Antibody level after exposures

Vaccine first?

No vaccine Vaccine given

Expose to pathogen Reset

No exposure yet. Choose “No vaccine” or “Vaccine given”, then press Expose to pathogen.

2. Bacteria under an antibiotic course

sensitive cell resistant cell killed cell

Stop early Run the full course

Let survivors multiply Resample cells Reset

Press Stop early or Run the full course to treat the population. The cells start with a few resistant ones.

Assumptions in this sketch: 40 cells; each starts resistant with a 5 in 100 chance (samples with no resistant cell are redrawn); each round kills a sensitive cell with a 65 in 100 chance and never kills a resistant cell; a full course is 6 rounds, stopping early is 2 rounds; no cell changes kind; survivors divide once. Panel 1: a first meeting peaks at 30 after 14, a later meeting at 100 after 5, in relative units; the curve shape is drawn, not measured.

Rule to keep: the first meeting with an antigen gives a slow response and leaves memory cells, so a later meeting is faster and larger; an antibiotic kills the sensitive bacteria it reaches, and the resistant ones are left to multiply (vaccines do not work perfectly in everyone, and how long a course should last is decided by doctors).

Try this.

1. Predict whether antibody rises faster on the first exposure or the second. Run both and compare the peaks.
2. Run the same two exposures with the vaccine switched on. Predict which exposure now behaves like a “second” one.
3. Start the antibiotic course and stop it early. Predict which kind of cell is left at the end.
4. Run the full course. Predict whether every cell is gone, then check which cells are left.

Explain: germ theory changed how people stop disease

A microbe is a living thing too small to see without a microscope, such as a bacterium. The germ theory of disease says that many diseases are caused by microbes that get into the body. A microbe or virus that causes disease is called a pathogen. Germ theory explains infectious diseases, not every illness; most heart disease is not an infection.

Later in the 1800s, experiments by Louis Pasteur, Robert Koch and others linked particular microbes to particular diseases. Once people accepted germ theory, they had a reason for practices that block microbes from passing from one person to another:

• Sanitation is keeping places clean and removing sewage and waste, so pathogens do not reach drinking water or food.
• Safe handling of food and water includes cooking, refrigeration and treating drinking water. Pasteurization is heating a food such as milk for a set time to kill harmful bacteria.
• Aseptic technique is a set of steps that keep microbes out of a wound or sterile area, such as clean hands, sterile gloves and sterile tools.
• Vaccination prepares the immune system before a pathogen arrives (next section).
• Chemicals and processes that destroy microbes. Disinfectants such as chlorine kill many microbes on surfaces, though some bacterial spores survive. Sterilization is a process that removes all forms of microbial life from an object, often with high-pressure steam.

Some of these habits came first: Semmelweis began chlorine washing in 1847 without knowing which microbe was involved. Germ theory explained why it worked.

Explain: vaccines and immune memory

A vaccine is a preparation that teaches the immune system to recognize a pathogen without causing the full disease. It works through an antigen, a substance the immune system can recognize and respond to, often a protein on a pathogen’s surface. The immune system responds by making antibodies, proteins that stick to one antigen and help destroy or block it.

Kind of vaccine	What is in it	Example
Live weakened	A weakened form of the virus or bacterium	MMR (measles, mumps, rubella)
Killed (inactivated)	Whole microbes killed by heat or chemicals	Some flu shots
Toxoid	A bacterial toxin made harmless	Tetanus, diphtheria
Subunit	One piece, such as a protein or sugar	Some pneumonia vaccines
mRNA	Instructions your cells use to make one viral protein	COVID-19 mRNA vaccines

The first time your body meets an antigen, the response is slow, often taking a week or more to build. During it, some immune cells become memory cells, which stay in the body long after. On a later exposure, memory cells recognize the antigen and quickly make large amounts of antibody. A vaccine gives you that first meeting without the disease, so the real pathogen meets the faster response.

A wanted poster is one way to picture this, but the immune system does not look at anything; memory cells carry receptors that fit one antigen.

Vaccines do not work perfectly in everyone: a small share of vaccinated people still get measles.

Explain: antibiotics and why they stop working

An antibiotic is a drug that kills bacteria or stops them from growing and dividing. Many antibiotics block the building of the bacterial cell wall. Others jam bacterial ribosomes, so the cell cannot make proteins. Your cells have no cell wall, and their ribosomes differ enough that these drugs mostly leave them alone.

A virus has no cell wall and no ribosomes of its own. It uses the ribosomes of the cell it infects, as Living or Not? explains. So antibiotics do not treat colds, flu or other viral infections.

Antibiotic resistance is the ability of some bacteria to survive a drug that kills others of their kind. It belongs to the bacteria, not to the person. In a large population of bacteria, a few may already carry a gene that lets them survive. An antibiotic kills or stops the sensitive ones, and the resistant ones are left to multiply. This is natural selection, the process in which individuals with a helpful trait survive and reproduce more, covered in Variation and Survival. Resistant bacteria can also pass resistance genes to other bacteria.

Health agencies say misuse of antibiotics, such as using them for a cold, can add to resistance: the bacteria in the body meet the drug with no benefit, which favors resistant ones. How long a course should last is decided by doctors, and for some infections, studies have found that shorter courses work as well as longer ones. The simulation’s “stop early” switch is a model of selection, not medical advice.

Elaborate: two clinics, then a nation

Time	Clinic	Deaths	Women counted	Deaths per 100 women
1841	First	237	3,036	7.81
1841	Second	86	2,442	3.52
1842	First	518	3,287	15.76
1842	Second	202	2,659	7.60
1846	First	459	4,010	11.45
1846	Second	105	3,754	2.80
April 1847	First	57	312	18.27
May 1847 (washing begins mid-month)	First	36	294	12.24
June 1847	First	6	268	2.24

Counts for 1841, 1842 and 1846 are from Semmelweis’s 1861 book (English translated excerpt, Table 1); the April and May 1847 counts are in Semmelweis’s book, and the June count is from Broemeling’s tabulation of his records (Broemeling prints 2.38 per 100 for June, but 6 ÷ 268 is 2.24). The last column was calculated here as deaths ÷ women counted × 100. In 1848, a full year of washing, the First Clinic recorded 45 deaths among 3,556 women, about 1.27 per 100.

Year	Reported U.S. measles cases
1962	481,530
1968	22,231
2000	85

These are reported cases from the CDC’s historical measles dataset. A vaccine became available in 1963. Before then, the CDC estimates, 3 to 4 million people in the United States were infected each year, though only about 500,000 cases a year were reported. Measles elimination was declared in 2000. Elimination means no continuous spread inside the country for at least 12 months, not zero cases.

1. In every year shown before 1847, which clinic had the higher death ratio? About how many times higher was it in 1846?
2. Why is “deaths per 100 women” a fairer comparison than the number of deaths alone?
3. Reported measles cases fell from 1962 to 1968. Why might the true number of infections be higher than any number in the table?

Design problem

A company has a new vaccine against a made-up disease that spreads in schools. Plan a fair test of whether it reduces cases of the disease. Name your groups, what you keep the same, what you count, how many people you need, and how you protect the volunteers.

One way to do it

• Groups: chance assigns volunteers to the vaccine or to a look-alike placebo shot, which tends to make the groups alike in age, health and habits.
• Independent variable: vaccine or placebo.
• Dependent variable: the number of confirmed cases in each group, defined before the trial starts (for example, symptoms plus a positive lab test).
• Constants: same dose schedule, follow-up time and illness checks in both groups.
• Blinding: neither volunteers nor the people judging illness know who got which shot, so expectations do not change the count.
• Sample size: thousands of volunteers, because a small trial may see too few cases of an uncommon disease to tell the groups apart.
• Ethics and safety: every volunteer gives informed consent and can leave at any time. An independent group watches for side effects and can stop the trial. Results are reported either way.
• What would mean what: far fewer cases in the vaccine group than the placebo group supports the vaccine. Similar numbers would mean no clear effect.

Evaluate: check your thinking

The First Clinic lost more mothers because examiners carried something deadly on their hands, often from autopsies. Chlorine washing removed it, and deaths fell sharply. Germ theory later explained why: many diseases are caused by microbes, and blocking or destroying them prevents illness.

Science practices you used: making predictions and testing them in a model, reading data tables and calculating ratios, comparing groups fairly, planning a blinded trial with a control group, and naming the limits of historical data.