Louis Pasteur

How to use this course

Louis Pasteur trained as a chemist and physicist and never qualified in medicine, yet his name is attached to milk, vaccines and an institute that has produced several Nobel laureates. The thread through his career is a method: a sharp question, a decisive experiment, and a willingness to follow a result from the crystal bench to the wine cellar, the silkworm nursery, the sheep pen and the hospital.

Each technical lesson opens with a paragraph for the general reader, then gives precise statements, derivations and exercises with folded solutions. Where Pasteur’s own concepts have since been sharpened, for example by the tetrahedral carbon of 1874 or by modern biochemistry, the lessons say so and use the modern form alongside his.

Timeline

Dole, Arbois, Besançon, 1822–1843

Louis Pasteur was born on 27 December 1822 in Dole, in the Jura, the third child of Jean-Joseph Pasteur and Jeanne-Étiennette Roqui. His father was a tanner who had served in Napoleon’s army, and the family was Catholic, modest and close. After a short stay at Marnoz, they settled in 1827 at Arbois, a small wine town by the river Cuisance, where the father ran a tannery. Arbois remained Pasteur’s home town all his life. He kept a house and later a laboratory there, and he did some of his experiments on wine in its cellars.

At the Arbois school he was an ordinary pupil. What stood out was his talent for drawing: as a teenager he made pastel portraits of family and neighbours, careful and observant, which survive. The headmaster saw ambition in him and suggested the École normale supérieure, the elite school for future teachers and scholars. In October 1838 he left for a preparatory boarding school in Paris, became so homesick that his father fetched him home within weeks, and finished his secondary studies closer to home.

Besançon and the entrance examination

From 1839 he attended the Collège royal de Besançon, earning a bachelor of letters in 1840 and working as a junior supervisor to pay his way. His science results were mediocre at first. He passed the bachelor of mathematical sciences at Dijon in 1842, with a weak mark in chemistry, and was admitted to the École normale that year, but low on the list. He chose to wait, spent another year preparing in Paris at the Lycée Saint-Louis, and in 1843 entered the school with a much better rank. The episode is typical: Pasteur was not precocious, but he was stubborn, methodical and unwilling to accept second best.

The École normale and the tartrates, 1843–1854

In Paris Pasteur went to the Sorbonne to hear Jean-Baptiste Dumas, the great lecturer of French chemistry, and came out of the lectures with a vocation. He also studied with Jean-Baptiste Boussingault at the Conservatoire des arts et métiers. He took his licence in 1845. In 1846 he was named to teach physics at the lycée of Tournon, but Antoine Jérôme Balard, the discoverer of bromine and professor at the École normale, kept him in Paris as a laboratory assistant. Balard’s laboratory was briefly shared with Auguste Laurent, one of the boldest theorists of chemical structure, and Pasteur followed the crystallography lectures of Gabriel Delafosse at the Sorbonne. From Laurent he took the habit of looking at crystals closely.

In 1847 he received the doctorate in sciences with two theses: one in chemistry on arsenites, and one in physics on the rotatory polarization of liquids. The physics thesis shows him already working with Jean-Baptiste Biot’s polarimeter and Biot’s laws.

The discovery of 1848

The puzzle came from Eilhard Mitscherlich. In 1844 Mitscherlich reported that sodium ammonium tartrate and sodium ammonium paratartrate (racemate) had the same composition, the same crystal form and the same angles, yet only the tartrate rotated polarized light in solution. Pasteur had noticed that tartrate crystals carry small extra facets, which crystallographers called hemihedral because they occur on only half of the corners that symmetry would predict, and that in tartrates they always face the same way. He expected to find that the paratartrate lacked them. Instead, in the spring of 1848, he found that its crystals carried hemihedral facets too, but some faced to the right and some to the left. He sorted the two kinds by hand under a lens, dissolved each, and put them in the polarimeter. One solution turned the light to the right, exactly like ordinary tartaric acid; the other turned it to the left by the same amount. Mixed in equal weights, they were inactive again. He announced the result to the Académie des sciences in May 1848.

Biot, who had studied tartaric acid for years, was sceptical. As the Biot course tells it, he made Pasteur repeat the separation before him with materials Biot supplied, prepared the solutions himself and looked through the polarimeter. The left-handed solution turned the light strongly to the left. Pasteur later recalled Biot taking his arm with emotion. From then on Biot was his patron.

Strasbourg

After a short appointment at the Dijon lycée, Pasteur became a substitute professor of chemistry at Strasbourg. There he courted Marie Laurent, daughter of the rector of the academy, and married her on 29 May 1849. Marie became his secretary, scribe and closest collaborator. They had five children: Jeanne (born 1850), Jean-Baptiste (1851), Cécile (1853), Marie-Louise (1858) and Camille (1863). At Strasbourg Pasteur pursued molecular asymmetry through asparagine, aspartic and malic acids, travelled through Germany and Austria in 1852 in search of the origin of racemic acid, and in 1853 produced it himself from tartaric acid (Lesson 05). The Société de pharmacie gave him a prize of 1,500 francs, and he received the Legion of Honour. He was made full professor in 1852.

Lille and the rue d’Ulm, 1854–1867

In 1854 Pasteur became professor of chemistry and dean of the new Faculty of Sciences at Lille, an industrial city of distilleries and breweries. In his inaugural address that December he spoke on the value of theory for practice, with the line that has followed him ever since: in the field of observation, “le hasard ne favorise que les esprits préparés” (chance favours only prepared minds). The faculty taught evening classes for workers and took students on tours of factories.

In 1856 a local manufacturer, Bigot, asked for help with batches of beet alcohol that had soured. Under the microscope Pasteur found that the healthy vats contained round yeast cells and the spoiled ones smaller rod-shaped bodies, and that the sour vats contained lactic acid. He turned the observation into a research programme. The 1857 memoir on lactic fermentation argued that each fermentation is the work of a specific living organism (Lesson 06). The Royal Society awarded him the Rumford Medal in 1856 for his work on crystals and polarized light.

Administrator in Paris

Late in 1857 he returned to the École normale as administrator and director of scientific studies. He tightened examinations and discipline, and his authoritarian style provoked student protests in the 1860s; he left the administration in 1867. For research he had at first only two attic rooms, which he fitted out at his own cost. There he extended the fermentation work, discovered organisms that live without free oxygen (1861), and fought the controversy over spontaneous generation (Lesson 07). From 1863 to 1867 he also taught geology, physics and chemistry at the École des Beaux-Arts. In 1862, after two failed attempts, he was elected to the Académie des sciences in the mineralogy section, on the strength of the crystal work.

Grief and duty

These were also years of loss. His daughter Jeanne died of typhoid fever in 1859, aged nine. Camille died in 1865 aged two, and Cécile of typhoid in 1866 aged twelve. Pasteur’s father died in 1865. Biographers have linked his later concentration on infectious disease to these deaths, though he never said so directly. In 1863 Napoleon III asked him to study the diseases of wine, a matter of national trade, and in 1865 Dumas asked him to save the silk industry of southern France. Both commissions, the first leading to pasteurization and the second to the study of disease in living animals, pushed his work toward medicine.

Optical activity and molecular dissymmetry

For the general reader. Your hands are mirror images, but you cannot superpose one on the other. Pasteur discovered that molecules can be handed in the same way. Two substances can be built from exactly the same atoms, melt at the same temperature and dissolve equally well, yet differ as left differs from right. The clue was light: a solution of one hand turns the plane of polarized light to the right, the other to the left.

From Biot’s laws to a molecular property

Biot had shown that the rotation produced by a solution obeys \(\alpha=[\alpha]\,l\,c\), with \(l\) the path length in decimetres and \(c\) the concentration in grams per millilitre, and that rotations of several active substances add. Because rotation persisted in solution and even in vapour, Biot concluded that it belonged to the individual molecule. Quartz is different: it rotates light as a crystal but not when melted or dissolved, so its activity belongs to the crystal lattice. Pasteur asked what feature of an individual molecule could produce rotation, and connected it to the external form of the crystal it builds.

Pasteur called the property dissymétrie moléculaire. The word chirality, from the Greek for hand, was introduced by Lord Kelvin in a lecture of 1893 and became standard in chemistry in the twentieth century. Pasteur could not say which arrangement of atoms was dissymmetric. He suggested a spiral or an irregular tetrahedron. The answer came in 1874, when Jacobus Henricus van ’t Hoff and Joseph Achille Le Bel independently proposed that the four bonds of carbon point to the corners of a tetrahedron. A carbon bearing four different groups is then chiral (Lesson 05).

A precise definition

An improper rotation \(S_n\) is a rotation by \(2\pi/n\) followed by reflection in the plane perpendicular to the axis. A mirror plane is \(S_1\) and an inversion centre is \(S_2\).

Proof sketch. Let \(\sigma\) be any reflection. The object \(M\) is superposable on its mirror image \(\sigma M\) exactly when there is a proper rotation \(R\) with \(R\sigma M=M\). The product \(R\sigma\) is an orthogonal map of determinant \(-1\) fixing a point, and every such map in three dimensions is an improper rotation \(S_n\) (for some angle). So \(M\) is achiral exactly when its symmetry group contains an improper element. For molecules that interconvert rapidly between conformations, the criterion is applied to the time-averaged structure, or equivalently to whether some accessible conformation is achiral.

Measuring composition

If a sample contains masses \(m_+\) and \(m_-\) of the two enantiomers, Biot’s additivity gives an observed specific rotation \([\alpha]_{\rm obs}=[\alpha]\,(m_+-m_-)/(m_++m_-)\). Chemists define

and the two coincide when the rotation is strictly additive. (Small deviations, from association between the enantiomers in solution, are known.) For natural (+)-tartaric acid in water, \([\alpha]_D\approx+12^\circ\) at 20 °C; the value depends noticeably on concentration and temperature, one reason Biot spent so long on this acid.

Resolution, mesotartaric acid, stereoisomers

For the general reader. Separating crystals with tweezers works only for rare substances in rare conditions. Between 1853 and 1858 Pasteur found two better ways to separate left and right molecules: pair them with a natural handed molecule, or let a living organism eat one hand and leave the other. Both methods are still used in the pharmaceutical industry, where the two hands of a drug can act very differently in the body.

Spontaneous resolution, and luck

Most racemates crystallize as a racemic compound, with both enantiomers in one crystal lattice. A minority crystallize as a conglomerate, a mechanical mixture of separate right- and left-handed crystals, and only these can be sorted by hand. Sodium ammonium tartrate is a conglomerate only below about 27 °C; above that temperature it crystallizes as a racemic double salt. Pasteur had chosen his salt well and worked in a cool Paris laboratory. He knew the role of chance in the result and later said so himself.

Diastereomeric salts (1853)

In May 1853, heating the tartrate of cinchonine (an alkaloid of cinchona bark) at about 170 °C for several hours, Pasteur converted ordinary tartaric acid into racemic acid, and found among the products a new, optically inactive tartaric acid that could not be resolved. In the same memoir he described a general method of resolution. Combine the racemic acid with an optically active base \(B^*\). The salts formed by the two enantiomers are

This is the reason a chiral environment, such as a living cell built from one-handed proteins, distinguishes the two hands of a molecule while a flask of achiral reagents does not.

Biological resolution (1858)

In 1858 Pasteur reported that when a micro-organism (probably a Penicillium mould) grew in a solution of ammonium paratartrate, the solution, at first inactive, gradually turned polarized light to the left. The organism consumed the right-handed tartrate and left the left-handed form. This was the first demonstration that living things discriminate between enantiomers, now called enantioselectivity. Pasteur drew a sweeping conclusion: the dissymmetric molecules of life are produced only by living things or under the action of dissymmetric forces. He spent years trying to impose handedness on chemical reactions with magnets, rotating mechanisms and reversed sunlight, without success.

Counting stereoisomers

Van ’t Hoff and Le Bel’s tetrahedral carbon made Pasteur’s dissymmetry concrete. A carbon bonded to four different groups is a stereocentre with two possible configurations, labelled R and S today.

Proof sketch for \(n\) even. Write a configuration as a string \(s=(s_1,\dots,s_n)\) of R and S. Reading the molecule from the other end reverses the string and leaves the molecule unchanged; reflecting swaps every R with S. A molecule is meso when \(s\) equals the swapped reversal of itself, which fixes the second half of the string by the first: \(2^{n/2}\) strings. Counting strings up to reversal (Burnside’s lemma with the group of order 2: \((2^n+2^{n/2})/2\)) gives the number of distinct molecules, \(2^{n-1}+2^{n/2-1}\). Among the \(2^{n/2}\) meso strings, reversal pairs them up, giving \(2^{n/2-1}\) meso molecules. For tartaric acid, \(n=2\): three stereoisomers, the (+) and (−) acids and Pasteur’s inactive mesotartaric acid.

Fermentation as life without air

For the general reader. In 1850 the leading chemists, Justus von Liebig and Jöns Jacob Berzelius among them, held that fermentation was a chemical breakdown, set off by decaying matter, in which yeast was at most a catalyst or by-product. Pasteur argued that fermentation is something living cells do in order to live. Each kind of fermentation has its own organism, and some organisms can live without air by fermenting.

Pasteur coined the terms aerobic and anaerobic. His careful analyses of wine fermentation also showed that it was not the simple reaction written by Joseph Louis Gay-Lussac, because a few percent of the sugar always appeared as glycerol and succinic acid. The by-products were evidence of a living process, not a clean chemical reaction. In 1897, two years after Pasteur’s death, Eduard Buchner obtained fermentation with a cell-free yeast extract, showing that the agents are enzymes made by the cells. The two views were reconciled: the cell makes the catalysts, and the cell lives by the reaction.

Mass balances

Why air reduces fermentation

In modern terms, fermentation of one glucose by glycolysis yields a net 2 ATP, while complete respiration to \(\mathrm{CO_2}\) and water yields about 30 to 32 ATP. A cell that needs a fixed amount of ATP to grow must ferment roughly fifteen times as much sugar when deprived of oxygen as it must burn when oxygen is available.

Brewer’s yeast complicates this: at high sugar it ferments even in air (the Crabtree effect, described in 1929). The Pasteur effect is clearest at low sugar concentrations.

Spontaneous generation and heat

For the general reader. If broth left in the open soon swarms with microbes, where do they come from? Many naturalists thought they arose from the broth itself. Pasteur showed that they come from germs carried in the air and on surfaces, and that a boiled liquid protected from those germs stays sterile indefinitely. The same reasoning tells us how hot and how long to heat wine, milk or surgical instruments.

The controversy with Pouchet

In 1858 Félix-Archimède Pouchet, director of the natural history museum in Rouen, reported that micro-organisms appeared in boiled hay infusions exposed only to artificial air. The Académie des sciences offered the Alhumbert Prize for experiments that would settle the question. Pasteur’s memoir of 1862 on organized corpuscles in the atmosphere won it. He filtered air through guncotton, dissolved the cotton and found under the microscope bodies identical to the germs of microbes. He sealed boiled broth in flasks and opened them in different places: in 1860, of twenty flasks opened along the lanes near Arbois, eight became contaminated, while on the Mer de Glace, above Chamonix, only one of the flasks he opened did so. Dust-free mountain air carried fewer germs.

The design answered the objection that boiling or sealing destroys some vital property of the air: the air is present and unheated. At a celebrated lecture at the Sorbonne on 7 April 1864 Pasteur showed flasks that had remained sterile for years. In 1864 a commission of the Académie judged in his favour after Pouchet withdrew from a public test. Pasteur’s results were not universal, however. Hay infusions sometimes defeated boiling, and in 1876–77 John Tyndall and Ferdinand Cohn showed why: hay carries bacterial spores that survive boiling. Tyndall’s answer was repeated heating, now called tyndallization.

Germs as a Poisson process

If viable germs are scattered randomly in air at a mean density \(\lambda\) per litre, the number entering a flask that takes in \(V\) litres is Poisson with mean \(\lambda V\). The flask stays sterile with probability

Heat: pasteurization

Pasteur’s patent of 1865 protected wine by heating it briefly to between about 50 and 60 °C, enough to kill spoilage organisms without ruining the taste. Later engineering gave the procedure a quantitative form. At a fixed temperature the number of surviving cells falls exponentially:

The decimal reduction time \(D\) is the time to kill 90 percent of the population; \(z\) is the temperature rise that divides \(D\) by ten. Two treatments are equivalent when they achieve the same number of decimal reductions \(t/D(T)\).

The germ theory of disease

For the general reader. If specific germs cause specific fermentations, perhaps specific germs cause specific diseases. Others had suggested this, but Pasteur and Robert Koch turned the idea into a science between 1865 and 1882. Pasteur came to it through silkworms; Koch through anthrax in cattle. Their methods differed and they became bitter rivals, but together they established that infectious diseases are caused by living micro-organisms.

Silkworms, 1865–1870

From 1865 Pasteur spent five seasons at Alès in the Cévennes, with his wife, his daughter Marie-Louise and young assistants including Émile Duclaux. The silk industry was being ruined by pébrine, a disease marked by dark spots and microscopic corpuscles in the worms. Pasteur at first doubted the corpuscles were the cause; by 1867 he recognized them as parasites and separated pébrine from a second disease, flacherie. His remedy was practical: each female moth lays her eggs on a separate cloth, then is crushed and examined under the microscope. Eggs from moths with corpuscles are burned. The method saved much of the industry. (The corpuscles are now known to be the microsporidian Nosema bombycis.)

Anthrax and serial culture

In 1876 Robert Koch described the life cycle of the anthrax bacillus, including its resistant spores. Critics still argued that some unseen agent in the blood, carried along with the bacillus, might be the true cause. In 1877 Pasteur and Jules Joubert answered by serial culture. A drop of anthrax blood is grown in sterile urine, a drop of that culture seeds a new flask, and so on through many passages. After enough passages the original blood is diluted far beyond the presence of a single molecule, yet the last culture kills as surely as the first. Only something that multiplies can survive such dilution. In 1878, with Joubert and Charles Chamberland, Pasteur published The germ theory and its applications to medicine and surgery, urging surgeons to flame instruments and boil dressings. Joseph Lister had already applied Pasteur’s fermentation work to surgery from 1867 and wrote to thank him.

Pasteur’s serial culture is a liquid-medium version of postulates 2 and 3. Koch’s solid media (gelatin, then agar plates) made pure cultures much easier to guarantee, a point he pressed in his polemics against Pasteur. The postulates are sufficient rather than necessary: they fail for asymptomatic carriers and for agents, like the rabies virus, that cannot be grown outside cells.

Attenuation: chicken cholera and anthrax

For the general reader. Edward Jenner had protected people against smallpox in 1796 with cowpox, a related and naturally mild disease. Pasteur showed that one could make the mild version in the laboratory. A germ grown under unfavourable conditions loses its virulence, and the weakened germ protects against the strong one. He called such preparations vaccines, in Jenner’s honour.

Chicken cholera, 1879–1880

Pasteur obtained the chicken cholera bacterium from the veterinarian Henry Toussaint and grew it in chicken broth. In the autumn of 1879 hens inoculated with an old culture, left standing for weeks, fell ill and recovered; later inoculated with a fresh, virulent culture, they survived. Pasteur reported the result to the Académie in February 1880 and introduced the word attenuation. He attributed the loss of virulence to exposure to the oxygen of the air over time.

Anthrax, 1880–1881

In July 1880 Toussaint reported an anthrax vaccine made by treating infected blood with heat and carbolic acid. Pasteur disputed it. His laboratory found that the anthrax bacillus grown at about 42–43 °C stops forming spores and gradually loses virulence. On 21 March 1881 he announced successful vaccination of sheep, and accepted a public challenge from the Agricultural Society of Melun.

Pasteur’s laboratory notebooks, opened to scholars in the 1970s and analysed by the historian Gerald Geison, show that the vaccine used in the trial was prepared by Chamberland and Émile Roux with potassium dichromate, a chemical method close to Toussaint’s, rather than by the oxygen method Pasteur described in public. The trial’s outcome is not in doubt; the controversy is about Pasteur’s candour and his treatment of a rival. Exercise 9.2 asks what the trial proved.

Rabies

For the general reader. Rabies is almost always fatal once symptoms appear, but it takes weeks or months to travel from the bite to the brain. Pasteur could not see the agent, a virus far too small for any microscope of his time, and could not grow it in broth. He grew it instead in the nervous systems of rabbits, weakened it by drying, and used the long incubation to immunize people after they had been bitten.

Fixed virus and dried cords

Working from 1880 with Roux and Chamberland, Pasteur found that rabies could be transmitted reliably by injecting nervous tissue from a rabid animal directly under the dura mater of the brain. Passed from rabbit to rabbit, the agent became adapted to the rabbit and its incubation period shortened to about a week and then stayed constant: the virus fixe. Roux had found that the infectivity of a rabbit’s spinal cord declined as it dried; Pasteur and Roux suspended strips of infected cord in sterile flasks over caustic potash, which absorbs moisture. A cord dried for about two weeks was no longer infective; cords dried for fewer days were progressively more so.

On 6 July 1885 Joseph Meister, aged nine, from Alsace, was brought to Paris two days after being badly bitten by a rabid dog. Pasteur was not a physician and did not inject the boy himself; the physicians Alfred Vulpian and Jacques-Joseph Grancher examined him and Grancher gave the injections, thirteen over about ten days. Meister did not develop rabies. In October Pasteur treated Jean-Baptiste Jupille, a young shepherd who had been bitten while defending other children. Pasteur announced the method to the Académie on 26 October 1885 and patients came from across Europe and as far as Russia and the United States. Within a year the laboratory had treated hundreds of bitten people. A public subscription for an institute to give the treatment followed (Lesson 11).

Geison’s reading of the notebooks showed that Pasteur had treated far fewer dogs after a bite than his public statements implied, and that two people had received related treatments earlier in 1885, one of whom may not have had rabies. The success with Meister was a calculated risk, which critics such as the physician Michel Peter attacked when treated patients died.

A race model

Let the virus need time \(T\) to reach the central nervous system, and let a vaccine started at time \(t_0\) after the bite produce protective immunity after a further delay \(\delta\). Treatment succeeds if \(t_0+\delta\lt T\). If \(T\) has a distribution with density \(f\), the probability of success is \(P(T>t_0+\delta)\). Bites on the face and head, closer to the brain, give shorter \(T\), which is why such cases were the most feared.

Stroke, war, and the Institut Pasteur, 1867–1888

In 1867 Pasteur took the chair of chemistry at the Sorbonne and obtained from the emperor a new laboratory of physiological chemistry at the École normale, which he directed until 1888. On 19 October 1868, aged 45, he suffered a cerebral haemorrhage that left his left side partly paralysed. He recovered his mind entirely, returned to Alès within months, but walked with difficulty and could no longer do fine manual work. From then on the hands at the bench belonged to assistants: Émile Duclaux, Jules Raulin, Jules Joubert, Charles Chamberland, Émile Roux, later Louis Thuillier, who died of cholera in Egypt in 1883 while studying the epidemic.

The Franco-Prussian War of 1870–71 hit him hard. His son Jean-Baptiste served in the army, and Pasteur travelled to find him during the retreat. In 1871 he returned the honorary doctorate in medicine that the University of Bonn had given him in 1868, with an angry letter, and he resolved that French beer should surpass German beer. Études sur la bière (1876) applied his fermentation methods to brewing. In 1874 the National Assembly voted him a life pension so that he could devote himself to research. The Royal Society gave him the Copley Medal the same year.

Honours and rivalry

He was elected to the Académie de médecine in 1873, where his lack of a medical degree, his certainty and his scorn for opponents made for stormy sessions. In 1881 he was elected to the Académie française, in the seat of Émile Littré, and he received the Grand Cross of the Legion of Honour. He met Robert Koch at the International Medical Congress in London in 1881. Their dispute became public at the hygiene congress in Geneva in 1882, inflamed by national feeling and by mistranslation; Koch attacked the reliability of Pasteur’s anthrax vaccine, and Pasteur replied in kind.

The Institut

After the rabies treatment of 1885, the Académie des sciences endorsed a plan for a rabies treatment centre. An international subscription raised several million francs, with gifts from emperors and from the poor alike. The Institut Pasteur, a private foundation for research, teaching and treatment, was inaugurated on 14 November 1888 in the rue Dutot in Paris, in the presence of the President of the Republic, Sadi Carnot. Its first departments were headed by Duclaux, Chamberland, Grancher, Roux and Élie Metchnikoff. Pasteur had suffered a second stroke in 1887 and could do little more himself; he lived in an apartment in the Institut.

Last years, death and legacy, 1888–1895

On 27 December 1892, his seventieth birthday, a jubilee was held for him in the great amphitheatre of the Sorbonne, in the presence of President Carnot and delegations from many countries. Joseph Lister spoke for the medical profession, and Pasteur’s address, read by his son because his voice was weak, called on young people to work in laboratories. Further strokes followed, and from 1894 he was largely an invalid. In 1895 he received the Leeuwenhoek Medal of the Royal Netherlands Academy. He died on 28 September 1895 at Villeneuve-l’Étang, in Marnes-la-Coquette near Paris, an annexe of the Institut where dogs were kept for rabies work. After a state funeral at Notre-Dame, his body was placed in a crypt beneath the Institut Pasteur, decorated with mosaics depicting his work. Joseph Meister later worked at the Institut as a caretaker.

The private science

Pasteur left instructions that his laboratory notebooks were not to be shown. His family kept them until his grandson Louis Pasteur Vallery-Radot gave them to the Bibliothèque nationale in 1964, and they were opened to researchers in the 1970s. Gerald Geison’s The Private Science of Louis Pasteur (1995) argued that Pasteur sometimes presented his work misleadingly, notably about the anthrax vaccine and the experimental basis for the rabies treatment. Max Perutz replied with a defence; later historians, including Patrice Debré, have treated Pasteur as a great scientist who was also combative, secretive and not above shading the record. The two views are compatible. The core results have held.

Legacy

• Chemistry: molecular chirality, resolution of racemates by crystals, by diastereomeric salts and by organisms; the link between chirality and life that runs through stereochemistry, biochemistry and drug design.
• Microbiology: the specificity of fermentations, anaerobic life, the refutation of spontaneous generation in its nineteenth-century form, and sterile technique.
• Medicine and industry: pasteurization, the germ theory as a guide for surgery and hygiene, laboratory attenuation of pathogens, and post-exposure rabies prophylaxis.
• Institutions: the Institut Pasteur and the international network of Pasteur institutes. Among those who worked there are Nobel laureates from Alphonse Laveran and Metchnikoff to François Jacob, André Lwoff, Jacques Monod, Luc Montagnier and Françoise Barré-Sinoussi.
• Honours in his lifetime included the Rumford (1856) and Copley (1874) medals of the Royal Society, of which he was a Foreign Member from 1869, the Albert Medal of the Royal Society of Arts (1882) and the Leeuwenhoek Medal (1895).

Sources and further reading

Biography

1. Louis Pasteur, Wikipedia (with extensive references).
2. Institut Pasteur, Institut Pasteur, history and Pasteur Museum pages.
3. G. L. Geison, Pasteur, Louis, in Dictionary of Scientific Biography, vol. 10, Scribner, 1974; online at Encyclopedia.com.
4. G. L. Geison, The Private Science of Louis Pasteur, Princeton University Press, 1995.
5. P. Debré, Louis Pasteur, Flammarion, 1994; English translation, Johns Hopkins University Press, 1998.
6. R. Vallery-Radot, La Vie de Pasteur, Hachette, 1900.
7. R. Dubos, Louis Pasteur: Free Lance of Science, Little, Brown, 1950.
8. M. Perutz, The pioneer defended, New York Review of Books, 21 December 1995.

Science

1. L. Pasteur, Recherches sur les relations qui peuvent exister entre la forme cristalline, la composition chimique et le sens de la polarisation rotatoire, Annales de chimie et de physique 24 (1848).
2. L. Pasteur, Transformation des acides tartriques en acide racémique. Découverte de l’acide tartrique inactif. Nouvelle méthode de séparation de l’acide racémique en acides tartriques droit et gauche, Comptes rendus 37 (1853), 162–166.
3. L. Pasteur, Mémoire sur la fermentation de l’acide tartrique, Comptes rendus 46 (1858), 615–618.
4. L. Pasteur, On the asymmetry of naturally occurring organic compounds (1860 lecture, English translation, Classic Chemistry, Le Moyne College).
5. L. Pasteur, Mémoire sur la fermentation appelée lactique, Comptes rendus 45 (1857), 913–916.
6. L. Pasteur, Mémoire sur les corpuscules organisés qui existent dans l’atmosphère, Annales de chimie et de physique 64 (1862).
7. L. Pasteur, Études sur le vin (1866), Études sur la maladie des vers à soie (1870), Études sur la bière (1876).
8. L. Pasteur, J. Joubert, C. Chamberland, La théorie des germes et ses applications à la médecine et à la chirurgie, Comptes rendus 86 (1878).
9. L. Pasteur, Méthode pour prévenir la rage après morsure, Comptes rendus 101 (1885).
10. Œuvres de Pasteur, ed. L. Pasteur Vallery-Radot, 7 vols., Masson, 1922–1939; digitized on Gallica.
11. Chiral resolution and Tartaric acid, Wikipedia.
12. J. Jacques, A. Collet, S. H. Wilen, Enantiomers, Racemates, and Resolutions, Wiley, 1981.