Historical Perspective: From Animalcules to Germ Theory and the Molecular Era

This chapter answers Section XL3.1 of XL3 Microbiology, one of the five optional sections of the Life Sciences (XL) paper: “Discovery of microbial world; Landmark discoveries relevant to the field of microbiology; Controversy over spontaneous generation; Role of microorganisms in transformation of organic matter and in the causation of diseases.” It follows the subject from the first sightings of microbes, through the experiments that ended spontaneous generation, to the proofs that microbes drive fermentation and the cycling of elements and that specific microbes cause specific diseases, and closes with the landmark discoveries up to the molecular era. Years are given where sources agree and rounded to the decade where they differ; GATE asks for the logic of an experiment far more often than for its year. The numericals are simple-lens magnification, rates and percentages from experimental data, and the stoichiometry of microbial mineralisation.

1. Discovering the microbial world

Robert Hooke's Micrographia (1665) used a compound microscope to illustrate, among much else, the fruiting structures of moulds, and gave biology the word cell for the boxes he saw in cork. Antonie van Leeuwenhoek, a cloth merchant of Delft, ground tiny single lenses and from the 1670s described, in letters to the Royal Society of London, the “animalcules” he saw in rainwater, pepper infusions and scrapings from his teeth. His drawings show rods, cocci, spirals and protozoa, so he is called the father of microbiology: the first person known to have seen bacteria and protozoa and recorded them carefully.

How could one bead of glass do this? A simple lens of focal length f gives an angular magnification of about M = D/f, where D = 250 mm is the near point of the eye. A bead lens with f = 1 mm magnifies about 250 times; Leeuwenhoek's best lenses reached a few hundred times. That is enough to see a 1–2 µm bacterium as a moving dot, though not to resolve its internal detail, because magnification and resolution are different things (resolution is taught with microscopy in XL3.2).

🎯 Why two centuries passed between seeing microbes and blaming them
Seeing is not proving. There was no way to grow one kind of microbe alone, no stains and no sterile technique, and as long as microbes were believed to arise spontaneously from decaying matter they looked like a product of decay and disease rather than its cause. The spontaneous-generation debate therefore had to be settled before germ theory could stand.

2. The controversy over spontaneous generation

Spontaneous generation (abiogenesis) held that living things arise from non-living matter; biogenesis holds that life comes only from pre-existing life. Each experiment below answered the objection raised against the one before it, which is exactly how GATE frames questions on it.

The experiments in sequence
WorkerDesignResult and what it left open
Francesco Redi (1668)Meat in open jars and in jars covered with gauzeMaggots only where flies could lay eggs; settled it for visible animals, not for microbes
John Needham (1740s)Broth boiled briefly, then corkedBroth turned cloudy, seeming to support spontaneous generation; heating was too short and the seal imperfect
Lazzaro Spallanzani (1760s)Infusions boiled longer in flasks sealed by melting the glassStayed clear; critics said heat destroyed a “vital force” and sealing shut out the air life needs
Louis Pasteur (1861)Broth boiled in swan-neck flasks open to air through a long S-shaped neckStayed sterile; breaking the neck or tilting broth into it gave growth. Air entered freely, so the vital-force objection failed; germs travel on dust
John Tyndall (1870s)Broths in a dust-free chamber; hay infusions boiled at lengthDust-free broths stayed sterile, but some hay infusions survived long boiling: heat-resistant forms exist

Tyndall's puzzle was solved when Ferdinand Cohn described heat-resistant endospores of Bacillus in the 1870s. Tyndall's remedy, intermittent heating (tyndallisation), boils the material, lets surviving spores germinate overnight into heat-sensitive cells, and boils again, repeated on three successive days. Pasteur also filtered air through cotton plugs and found under the microscope that the trapped dust carried bodies like those growing in spoiled broths.

⚠️ The swan neck did not exclude air, and that is its point
Spallanzani's sealed flasks failed to convince precisely because they excluded air. Pasteur's open, curved neck let air in while trapping dust in its bend, so the only variable between a sterile flask and a spoiled one was contact with dust-borne germs. Options claiming that the neck “kept air out” or that the flask was “sealed” are wrong.

3. Microbes transform organic matter

Fermentation. In the 1830s Cagniard de la Tour, Theodor Schwann and Friedrich Kützing independently concluded that yeast is a living organism responsible for alcoholic fermentation, while Justus von Liebig and other chemists held that fermentation was a purely chemical decomposition. Pasteur showed in the 1850s and 1860s that each fermentation has its own microbe: yeast makes ethanol, a different organism makes lactic acid, and butyric fermentation is carried out by organisms that live without air, which he called anaerobic. The “diseases” of wine came from contaminating microbes and were prevented by mild heating, the origin of pasteurisation. In 1897 Eduard Buchner fermented sugar with a cell-free yeast extract: the catalysts are enzymes that act outside the living cell, a result that settled the dispute and helped found biochemistry.

Cycling of elements. Sergei Winogradsky showed in the 1880s and 1890s that Beggiatoa oxidises H₂S to sulphur for energy and that nitrifying bacteria oxidise ammonia to nitrite and nitrite to nitrate while fixing CO₂: chemolithotrophy, life on inorganic energy sources. He isolated nitrifiers on media free of organic matter and devised the Winogradsky column. Martinus Beijerinck developed enrichment culture, isolating root-nodule bacteria and, in 1901, the free-living nitrogen fixer Azotobacter; Hellriegel and Wilfarth had shown in the 1880s that legumes fix atmospheric nitrogen only when their roots bear nodules. Together these founded microbial ecology: microbes mineralise the C, N, S and P of dead matter to CO₂, NH₄⁺, SO₄²⁻ and PO₄³⁻, which plants reuse.

🧠 Worked example: how much CO₂ does mineralisation release?
Complete aerobic oxidation: C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O. Take 18 g glucose (M = 180 g mol⁻¹) = 0.1 mol. It yields 0.6 mol CO₂ = 0.6 × 44 = 26.4 g and consumes 0.6 mol O₂ = 0.6 × 32 = 19.2 g. This oxygen demand is why organic waste discharged into a river depletes its dissolved oxygen as microbes decompose it.

4. Microbes as the cause of disease

Clues came first. Agostino Bassi showed in the 1830s that a fungus causes muscardine disease of silkworms, the first proof that a microbe causes an animal disease. Ignaz Semmelweis (Vienna, 1847) cut deaths from puerperal (childbed) fever by making doctors wash their hands in chlorinated lime before examining women; John Snow (London, 1854) traced a cholera outbreak to the Broad Street pump, founding epidemiology before the germ was known. Joseph Lister (1867) treated wounds, dressings and instruments with carbolic acid (phenol), founding antiseptic surgery. Pasteur moved from silkworm disease to attenuated vaccines against chicken cholera, anthrax (1881) and rabies (1885).

Robert Koch gave the proof. In 1876 he linked Bacillus anthracis to anthrax: the rods were in the blood of every diseased animal, grew outside the body, still caused anthrax when injected into mice, and formed spores that persist in soil. In 1882 he identified Mycobacterium tuberculosis, and later Vibrio cholerae. His laboratory brought solid media (gelatin, then agar, suggested by Fanny Hesse), the dish of his assistant Julius Petri (1887), and staining and photography of bacteria. Koch's postulates:

  • The microbe is found in every case of the disease and not in healthy hosts.
  • It is isolated from the diseased host and grown in pure culture.
  • The pure culture causes the same disease when inoculated into a healthy, susceptible host.
  • The same microbe is re-isolated from the experimentally infected host.
⚠️ Where the postulates break down
Healthy carriers (of Vibrio cholerae or Salmonella Typhi) break the first postulate. Pathogens that cannot be grown in cell-free media (Mycobacterium leprae, Treponema pallidum, all viruses) break the second. A disease with no animal model, or one that would be unethical to cause in people, blocks the third, and diseases needing two organisms together defy the one-microbe logic. Molecular Koch's postulates (Stanley Falkow, 1988) apply the same logic to a virulence gene: it is found in pathogenic strains, inactivating it reduces virulence, and restoring it restores virulence.
ℹ️ The Indian chapter of the story
Alphonse Laveran saw the malaria parasite in human blood in 1880. Ronald Ross, working in India, showed in 1897 that it develops in Anopheles mosquitoes, and received the Nobel Prize in 1902. Waldemar Haffkine developed cholera and plague vaccines in India in the 1890s; the Haffkine Institute in Mumbai carries his name.

5. Landmark discoveries

After germ theory the field branched into immunology, virology, chemotherapy and, in the twentieth century, microbial genetics. The table keeps only discoveries GATE builds on; each sits in the syllabus heading that teaches it in depth.

Landmarks after germ theory
WhenDiscovery and discovererWhy it matters
1796Smallpox vaccination with cowpox material (Edward Jenner)First vaccine, long before germs were known
1880sPhagocytosis (Élie Metchnikoff); Gram stain, 1884 (Hans Christian Gram)Cellular immunity; the main split of bacteria by wall type
1890Antitoxin against diphtheria and tetanus (Emil von Behring, Kitasato Shibasaburo)Humoral immunity and passive immunisation by serum
1892, 1898Tobacco mosaic agent passes bacteria-proof filters (Dmitri Ivanovsky); “contagium vivum fluidum” (Martinus Beijerinck); foot-and-mouth agent also filterable (Loeffler and Frosch, 1898)Discovery of viruses, plant and animal
1915, 1917Bacteriophages (Frederick Twort; Félix d'Hérelle)Phage became the model system of molecular biology
1910 to 1940sSalvarsan (Paul Ehrlich, 1910); penicillin (Alexander Fleming, 1928; purified by Florey and Chain); Prontosil (Gerhard Domagk, 1930s); streptomycin (Selman Waksman's laboratory, 1940s)Chemotherapy: synthetic drugs, then antibiotics; streptomycin was the first effective drug against tuberculosis
1928, 1944Transformation of pneumococci (Frederick Griffith); the transforming principle is DNA (Avery, MacLeod and McCarty)DNA is the genetic material
1946, 1961Bacterial conjugation (Joshua Lederberg and Edward Tatum); the operon (François Jacob and Jacques Monod)Bacteria have genetics; genes are regulated
1977, 1990Archaea recognised from 16S rRNA comparisons (Carl Woese and George Fox); three domains proposed (Woese and colleagues)Molecular phylogeny replaced shape-based classification
1980s, 2012PCR (Kary Mullis); CRISPR-Cas9 as a programmable DNA cutter (Emmanuelle Charpentier and Jennifer Doudna)Both are tools taken from microbes: a thermostable polymerase and a bacterial immune system
⚠️ Pairs that examiners swap
Fleming found penicillin; Waksman's laboratory found streptomycin. Ehrlich's Salvarsan is a synthetic arsenical, not an antibiotic. Ivanovsky showed filterability but still thought of a toxin or tiny bacterium; Beijerinck argued for a new kind of living agent. Griffith saw transformation; Avery's group identified DNA as its cause by showing the activity is destroyed by deoxyribonuclease but not by proteases or ribonuclease.

Key takeaways

  • Hooke (Micrographia, 1665) drew moulds and named the cell; Leeuwenhoek, from the 1670s, was the first to see and record bacteria and protozoa, with single lenses magnifying a few hundred times (M ≈ 250 mm / f).
  • Spontaneous generation fell step by step: Redi (visible animals), Needham's flawed broths, Spallanzani's sealed flasks (air objection), Pasteur's open swan-neck flasks (1861) and Tyndall's heat-resistant forms, explained by Cohn's endospores.
  • Pasteur tied each fermentation to its own microbe and introduced pasteurisation; Buchner's cell-free extract (1897) showed the catalysts are enzymes.
  • Winogradsky (chemolithotrophy, the Winogradsky column) and Beijerinck (enrichment culture, Azotobacter) showed microbes mineralise organic matter and drive the C, N and S cycles; 1 mol glucose oxidised gives 6 mol CO₂ and uses 6 mol O₂.
  • Germ theory: Bassi, Semmelweis (1847), Snow (1854), Lister (1867), then Koch's proof for anthrax (1876) and tuberculosis (1882). The four postulates fail for carriers, unculturable pathogens and diseases without a model; molecular postulates apply them to genes.
  • Landmarks: Jenner (1796), viruses (Ivanovsky 1892, Beijerinck 1898), phages (Twort, d'Hérelle), Ehrlich, Fleming (1928), Domagk, Waksman, Griffith and Avery (DNA), Lederberg and Tatum, Jacob and Monod, Woese (archaea, 1977), PCR and CRISPR-Cas9.

Practice questions (17)

Attempt each one before opening the answer. Every explanation names the tempting wrong option as well as the right one, because that is where marks are lost.

  1. Which worker first described bacteria and protozoa, seen through hand-ground single-lens microscopes, in letters to the Royal Society of London?

    1. Robert Hooke, whose Micrographia illustrated moulds and cork cells seen with a compound microscope
    2. Louis Pasteur, who studied the microbes of fermentation and of spoiled wine and broth
    3. Antonie van Leeuwenhoek, a Delft cloth merchant who ground his own tiny bead lenses
    4. Lazzaro Spallanzani, who boiled infusions in sealed flasks to test spontaneous generation
    Show answer

    Answer: C — Antonie van Leeuwenhoek, a Delft cloth merchant who ground his own tiny bead lenses

    Leeuwenhoek's letters to the Royal Society from the 1670s describe animalcules in rainwater, infusions and dental scrapings, including rods, cocci and spirals. Hooke is the tempting distractor: he used a compound microscope and illustrated moulds and cork cells, but did not report bacteria. Pasteur and Spallanzani worked a century and more later.
  2. A bead lens of the kind used in early single-lens microscopes has a focal length of 1.25 mm. Taking the magnification of a simple lens as M = D/f with D = 250 mm (the near point of the eye), the lens magnifies ____ times.

    Numerical answer — type the value.

    Show answer

    Answer: 200

    M = D/f = 250 mm ÷ 1.25 mm = 200. The shorter the focal length (the smaller and more strongly curved the bead), the higher the magnification, which is why Leeuwenhoek's tiny beads outperformed the compound microscopes of his day.
  3. Robert Hooke's Micrographia (1665) is remembered in microbiology because it

    1. illustrated the fruiting structures of a mould and introduced the word cell
    2. gave the first report of bacteria in scrapings taken from human teeth
    3. disproved the spontaneous generation of maggots by covering jars of meat
    4. described the first pure culture of a bacterium on a solid medium
    Show answer

    Answer: A — illustrated the fruiting structures of a mould and introduced the word cell

    Micrographia used a compound microscope to draw, among other things, a mould's sporangia and the empty boxes of cork, which Hooke called cells. Bacteria in dental scrapings are Leeuwenhoek's report, the covered jars are Redi's (1668), and pure culture on solid media came from Koch's laboratory two centuries later.
  4. Why did Pasteur's swan-neck flask experiment answer the objection that had been raised against Spallanzani's sealed-flask results?

    1. The neck was melted shut after boiling, so no microbe could reach the cooled broth at any time
    2. The broth was boiled far longer than before, which killed even the most heat-resistant spores
    3. The curved neck was packed with cotton, so the air reaching the broth had been filtered sterile
    4. Air reached the broth freely through the open neck while dust and germs settled in its bend
    Show answer

    Answer: D — Air reached the broth freely through the open neck while dust and germs settled in its bend

    Spallanzani's critics said sealing kept out the air (and a vital force) that life needs. Pasteur's neck stayed open, so air entered, yet the broth stayed sterile until dust trapped in the bend reached it. A sealed or cotton-plugged neck would have reopened the very objection he was answering, and long boiling was not the point of the design.
  5. A hay infusion boiled for one hour in a flask kept in a dust-free chamber becomes turbid after two days, while a meat broth boiled for five minutes in the same chamber stays clear. Which explanation fits both results and also points to a remedy?

    1. Hay holds a vital force that withstands boiling and generates new microbes once the infusion cools in still air
    2. Hay carries heat-resistant endospores; boiling on successive days, after they germinate, would sterilise it
    3. Dust-free air still carries vegetative bacteria, and these settle preferentially in the richer hay infusion
    4. Long boiling breaks hay sugars into products that later polymerise into turbid material with no microbes at all
    Show answer

    Answer: B — Hay carries heat-resistant endospores; boiling on successive days, after they germinate, would sterilise it

    Hay carries Bacillus endospores that survive an hour of boiling; meat broth lacks them, so a short boil sterilises it. Intermittent heating (tyndallisation) lets spores germinate between boilings and kills the heat-sensitive cells they become. Airborne bacteria cannot be the cause, because the meat broth in the same dust-free air stays clear, and the vital-force idea is the very claim the experiment refutes.
  6. In a repeat of Pasteur's swan-neck experiment with a nutrient broth, which of the following outcomes are expected?

    1. Boiled broth in a flask whose curved neck is left intact stays clear for months
    2. Boiled broth turns turbid within days once the neck is snapped off near the body of the flask
    3. Unboiled broth in a flask with an intact curved neck stays clear, because the neck traps all dust
    4. Boiled broth turns turbid after the flask is tilted so that broth runs into the bend of the neck and back
    Show answer

    Answer: A — Boiled broth in a flask whose curved neck is left intact stays clear for months; B — Boiled broth turns turbid within days once the neck is snapped off near the body of the flask; D — Boiled broth turns turbid after the flask is tilted so that broth runs into the bend of the neck and back

    The intact neck admits air but traps dust, so boiled broth stays sterile; removing the neck, or washing the trapped dust into the broth by tilting, brings germs in and the broth spoils. Unboiled broth already contains living microbes from its ingredients, so the neck cannot keep it clear; the experiment depends on boiling first.
  7. Eduard Buchner obtained alcoholic fermentation of sugar with juice pressed from ground yeast and filtered free of intact cells. What did this result show?

    1. Fermentation is catalysed by enzymes that stay active outside the living cell
    2. Fermentation needs intact living yeast cells, exactly as Pasteur had argued
    3. Fermentation is an uncatalysed decay of sugar needing no yeast material at all
    4. Yeast juice carries live bacteria that take over fermentation once yeast is broken
    Show answer

    Answer: A — Fermentation is catalysed by enzymes that stay active outside the living cell

    A cell-free extract still fermented, so the activity lies in molecules (Buchner's zymase, a mixture of enzymes) rather than in the living cell. That contradicted the strict vitalist reading of Pasteur, which is the tempting distractor, while also showing that yeast material is essential, against the idea of uncatalysed decay. The juice was filtered free of cells, so contaminating live bacteria are excluded.
  8. Winogradsky's studies of Beggiatoa and of nitrifying bacteria established which concept?

    1. Fermentation, using an organic compound as both electron donor and acceptor
    2. Symbiotic nitrogen fixation, reduction of N₂ to ammonia in root nodules
    3. Chemolithotrophy, gaining energy by oxidising inorganic H₂S, NH₃ or NO₂⁻
    4. Anoxygenic photosynthesis by purple and green sulphur bacteria in ponds
    Show answer

    Answer: C — Chemolithotrophy, gaining energy by oxidising inorganic H₂S, NH₃ or NO₂⁻

    Beggiatoa oxidises H₂S and nitrifiers oxidise ammonia and nitrite, using the energy to fix CO₂: chemolithotrophy, which Winogradsky discovered. Purple and green sulphur bacteria also use H₂S, which makes anoxygenic photosynthesis the tempting distractor, but they use it as an electron donor for light-driven growth, not as an energy source in the dark. Nodule nitrogen fixation was shown by others.
  9. Soil is incubated in air in a liquid medium of mannitol and mineral salts with no combined nitrogen. After several transfers into fresh medium, large aerobic cells able to fix N₂ dominate. The approach and the organism most likely enriched are

    1. Koch's pure-culture streaking, enriching the anaerobic nitrogen fixer Clostridium pasteurianum
    2. The Winogradsky column, enriching the light-dependent heterocystous cyanobacterium Anabaena
    3. Pasteur's fermentation method, enriching the acid-tolerant lactic acid bacterium Lactobacillus
    4. Beijerinck's enrichment culture, enriching the free-living aerobic nitrogen fixer Azotobacter
    Show answer

    Answer: D — Beijerinck's enrichment culture, enriching the free-living aerobic nitrogen fixer Azotobacter

    A medium lacking combined nitrogen favours N₂ fixers; aerobic incubation with an organic carbon source favours aerobic heterotrophs; serial transfer is the hallmark of Beijerinck's enrichment culture, by which he isolated Azotobacter in 1901. Clostridium pasteurianum fixes N₂ but is a strict anaerobe and would not thrive in aerated medium; Anabaena needs light, and Lactobacillus cannot fix N₂.
  10. Soil microbes completely oxidise 45 g of glucose (C₆H₁₂O₆) to CO₂ and water under aerobic conditions. Taking C = 12, H = 1 and O = 16, the mass of CO₂ released is ____ g.

    Numerical answer — type the value.

    Show answer

    Answer: 66

    C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O. M(glucose) = 6(12) + 12(1) + 6(16) = 180 g mol⁻¹, so 45 g = 0.25 mol. CO₂ formed = 6 × 0.25 = 1.5 mol, and M(CO₂) = 44 g mol⁻¹, so 1.5 × 44 = 66 g. Forgetting the factor 6 gives 11 g.
  11. Which observation conflicts specifically with Koch's first postulate, rather than with the second, third or fourth?

    1. Healthy people carry Vibrio cholerae in the gut without symptoms during an outbreak
    2. Mycobacterium leprae cannot be grown on any cell-free laboratory culture medium
    3. No animal species develops the human disease when inoculated with the cultured organism
    4. The organism recovered from an inoculated animal differs from the one that was inoculated
    Show answer

    Answer: A — Healthy people carry Vibrio cholerae in the gut without symptoms during an outbreak

    The first postulate demands the microbe in every case of the disease and not in healthy hosts; asymptomatic carriers break the second half of that requirement. Failure to grow M. leprae in culture violates the second postulate, the lack of an animal model the third, and a different organism on re-isolation the fourth.
  12. In an illustrative ward record, 600 of 5000 mothers died of puerperal fever in the year before doctors began washing their hands in chlorinated lime, and 90 of 4500 died in the year after. The relative reduction in the death rate is ____ % (to one decimal place).

    Numerical answer — type the value.

    Show answer

    Answer: 83.3

    Rate before = 600/5000 = 0.12 (12%). Rate after = 90/4500 = 0.02 (2%). Relative reduction = (12 − 2)/12 × 100 = 83.33%, which is 83.3 to one decimal place. The absolute reduction is 10 percentage points, a common slip; comparing raw deaths (600 to 90, 85%) ignores the different number of births.
  13. Treating wounds, dressings and surgical instruments with carbolic acid to prevent infection after operations was introduced by

    1. Ignaz Semmelweis
    2. Joseph Lister
    3. John Snow
    4. Robert Koch
    Show answer

    Answer: B — Joseph Lister

    Lister published his antiseptic method with carbolic acid (phenol) in 1867. Semmelweis is the tempting distractor, but his measure (1847) was handwashing in chlorinated lime before examining women in a maternity ward, not the treatment of surgical wounds. Snow traced cholera to a water pump, and Koch proved specific causes of anthrax and tuberculosis.
  14. Which of the following are genuine limitations of Koch's postulates as originally stated?

    1. Mycobacterium leprae and Treponema pallidum cannot be grown in cell-free culture media
    2. Some pathogens are carried by healthy people who never develop the disease
    3. Bacillus anthracis forms spores and can be cultured on solid media and injected into mice
    4. Deliberately infecting people to test the third postulate for a human-only pathogen is unethical
    Show answer

    Answer: A — Mycobacterium leprae and Treponema pallidum cannot be grown in cell-free culture media; B — Some pathogens are carried by healthy people who never develop the disease; D — Deliberately infecting people to test the third postulate for a human-only pathogen is unethical

    Unculturable pathogens block the second postulate, healthy carriers the first, and the ethics of human inoculation the third. The anthrax bacillus is not a limitation at all: it satisfied every postulate and was Koch's own model case in 1876.
  15. Ivanovsky's 1892 finding that sap from mosaic-diseased tobacco stayed infectious after passing through a filter that retains bacteria was important because it

    1. proved the disease was caused by a toxin secreted by bacteria multiplying in the leaves
    2. showed that the agent was a nucleic acid enclosed within a coat of protein subunits
    3. revealed an infectious agent smaller than any bacterium, later recognised as a virus
    4. showed that the agent could be grown in pure culture on nutrient agar like a bacterium
    Show answer

    Answer: C — revealed an infectious agent smaller than any bacterium, later recognised as a virus

    Passing a bacteria-proof filter showed an agent below bacterial size; Beijerinck (1898) then argued it was a new kind of agent that multiplies only in living tissue, and the word virus stuck. The toxin idea is the tempting distractor because Ivanovsky himself considered it, but his filtrate was never shown to contain a toxin. Its nucleic acid and protein make-up came decades later, and the agent cannot grow on agar.
  16. Which of the following discoverer–discovery pairs are correctly matched?

    1. Paul Ehrlich: Salvarsan, a synthetic arsenical drug against syphilis
    2. Selman Waksman's laboratory: penicillin from a Penicillium mould
    3. Gerhard Domagk: Prontosil, the first sulfonamide drug used clinically
    4. Emil von Behring and Kitasato Shibasaburo: antitoxin against diphtheria and tetanus
    Show answer

    Answer: A — Paul Ehrlich: Salvarsan, a synthetic arsenical drug against syphilis; C — Gerhard Domagk: Prontosil, the first sulfonamide drug used clinically; D — Emil von Behring and Kitasato Shibasaburo: antitoxin against diphtheria and tetanus

    Ehrlich's Salvarsan (1910), Domagk's Prontosil (1930s) and Behring and Kitasato's antitoxin (1890) are correctly paired. Penicillin was Fleming's discovery (1928); Waksman's laboratory found streptomycin, from Streptomyces, in the 1940s.
  17. An extract of heat-killed smooth (S) pneumococci converts live rough (R) cells into S cells. Portions of the extract are treated with single enzymes before being added to R cells. Which result identifies DNA as the transforming principle?

    1. Activity is lost after protease treatment but survives deoxyribonuclease treatment
    2. Activity is lost after deoxyribonuclease but survives protease and ribonuclease
    3. Activity is lost after ribonuclease treatment but survives deoxyribonuclease treatment
    4. Activity survives all three enzymes but is lost when the extract is heated to boiling
    Show answer

    Answer: B — Activity is lost after deoxyribonuclease but survives protease and ribonuclease

    If DNA carries the activity, only the enzyme that destroys DNA abolishes it, and enzymes that destroy protein or RNA leave it intact; this was the logic of Avery, MacLeod and McCarty (1944). Loss after protease would point to protein and loss after ribonuclease to RNA. Loss on boiling cannot discriminate, and the extract was made from heat-killed cells in the first place.