Defeating the Ministers of Death

by David Isaacs

  Pasteur’s background would have an impact on his approach to problems later in life. His preference was always to do his research in the field, often literally. The Jura was a region of traditional crafts and trades, like tanning – his father’s occupation – and winemaking, which had a chemical basis that intrigued the inquisitive Louis and which he studied and tried to improve.

  Yet Pasteur was a distinctly average student. He much preferred to sit on the riverbank, fishing or drawing. He went off to school in Paris at age 16, but returned after a month because he was homesick. A year later, in 1839, he went to college in nearby Besançon and obtained a Bachelor of arts degree in philosophy. He then obtained a Baccalauréat Scientifique (Bachelor of Science) – ironically with a poor grade in chemistry. First he was made Professor of Physics in 1848 and then Professor of Chemistry at the University of Strasbourg. Later Pasteur went to work in Paris, but he always returned to the field.

  Pasteur married the university rector’s daughter Marie in 1849 and they had five children. Marie was Pasteur’s greatest source of support academically, and also emotionally when their two beloved daughters and one of their sons died from typhoid in childhood. Louis dictated his manuscripts to Marie in the evenings and she prepared them for publication. Much as Pasteur contributed to the world, he would have been far less effective without Marie.

  Pasteur was an extraordinary scientist and thinker, and a great experimentalist in the laboratory and the field. As a chemist, he was the first person to recognise an important phenomenon we now call isomerism, which is the concept that the same molecule can exist in mirror-image forms, left- and right-handed. As a true Frenchman, he showed that fermentation worked better under anaerobic conditions (without air), and that the souring of wine that turned it to vinegar was caused by bacteria. He demonstrated that heating milk to only moderately high temperatures for a few minutes would kill any living micro-organisms and thus sterilise the milk. This sterilisation process, which was given the name pasteurisation, has played a major role in infection control and thus in vaccine manufacture.

  In 1865, the Department of Agriculture sought Pasteur’s help over a silkworm disease that was destroying the silk industry in France and Italy. He set up field laboratories and, over five painstaking years, established that the problem was due to infections and that the solution was to separate sick from healthy silkworms. Pasteur’s work rescued the silk industry and made him even more famous.

  Pasteur and immunisation

  With regards to immunisation, Pasteur was especially important as the first scientist to describe attenuation, the process (mentioned in Chapter 2) whereby a sample of disease bacteria or virus is weakened by heat, chemical treatment or other processes, and can then be used to inoculate people against the full-strength form of the disease. This discovery came from a serendipitous observation – although as Pasteur once said, with no trace of false modesty: ‘In the fields of observation, chance favours only the prepared mind.’

  While working on chicken cholera, a disease that could spread through a farmyard and wipe out an entire flock in three days, Pasteur was able to identify and grow the cholera bacillus (a rod-shaped bacterium). If he injected chickens with the bacillus they died within 48 hours.

  When Pasteur left Paris to escape the heat in the summer of 1879, he left his cultures on the laboratory shelf. After he returned and inoculated chickens with the stored bacilli, the chickens remained healthy. He and his team grew new cultures of the bacillus and tested them on new birds, as well as on those that had survived inoculation with the cultures from the shelf. The new birds all died, but the birds previously inoculated again remained healthy. Repeatedly growing the cultures had weakened, or attenuated, the bacilli, Pasteur realised. This in turn protected the inoculated birds against the virulent bacillus strain.

  Pasteur also recognised that his observations resembled those made some 80 years previously by Edward Jenner, and indeed (as mentioned earlier) it was Pasteur who coined the term ‘vaccination’ in honour of Jenner. Pasteur’s finding has been used to make attenuated viral vaccines like those currently used against measles, mumps, rubella and chickenpox.

  Pasteur next set his mind to the problem of anthrax, a disease decimating the sheep and cattle industries. The German physician–microbiologist Robert Koch, a rival and fierce critic of Pasteur, had isolated the anthrax bacillus, but it was Pasteur who proved that the organism was the cause of the disease.

  Typically making observations while walking in the country, Pasteur noticed that one corner of a field where sheep were grazing was a different colour from the rest. When he made inquiries, the farmer tending the pasture told him he had buried some sheep that had died from anthrax in that corner.

  Pasteur deduced that worms feeding on the carcasses of the infected sheep were bringing anthrax spores to the surface, and that sheep grazing on the contaminated soil were becoming infected. But stopping the sheep from feeding on contaminated soil would not be enough to prevent disease transmission, so Pasteur put his energy into developing a vaccine, attenuating the anthrax bacillus by oxidising and ageing it.

  The vaccine was promising in the laboratory, but a well-known veterinarian called Hippolyte Rossignol was sceptical and challenged Pasteur to test his vaccine in a public trial. Pasteur agreed.

  The venue for the trial was a farm called Pouilly-le-Fort south of Paris, the year 1882. The trial would involve 50 sheep; Pasteur would vaccinate half, and the other half, the control group, would remain unvaccinated. All the sheep would then receive a large, usually lethal dose of anthrax. The challenge was that all the control sheep had to die and all the inoculated sheep survive.

  The press had a field day (dad joke). Not only the French papers but also the London Times published daily bulletins. Excited crowds created a carnival atmosphere.

  They were not disappointed. Within two days, all 25 control sheep were dead and all 25 inoculated sheep still alive. One can imagine the headlines: ‘Pasteur Prevails in the Pasture’! This triumph did wonders for Pasteur’s reputation, but nothing for his humility.

  Over the next 10 years, 3.5 million sheep and 500,000 cattle were vaccinated against anthrax, of which more than 99% survived. Mass immunisation was born.

  Pasteur and Australia

  In 1888 Pasteur sent his assistant, Dr Adrien Loir, on a steamer from Paris to Sydney with cultures of chicken cholera. Loir was Madame Pasteur’s nephew (the word ‘nepotism’ derives from the popes’ practice of favouring their illegitimate sons, who were called their nephews, or nipoti in Italian). Loir and Pasteur had made a bid for a £25,000 prize offered by the New South Wales Government’s Intercolonial Rabbit Commission for anyone who could demonstrate a plausible way to eliminate rabbits.

  In 1859, an English settler called Thomas Austin had had 24 rabbits sent out from the United Kingdom and released them on his property, Barwon Park in Victoria, so he could hunt them for ‘sport’. By the time the rabbit commission was set up in 1887 – less than 40 years later – they had bred like, well, rabbits, numbering more than a billion and occupying over two-thirds of Australia.

  Pasteur and Loir’s rabbit proposal involved infecting rabbits with food laced with chicken cholera. The New South Wales Government set up a laboratory on Rodd Island in Iron Cove, Sydney, and it was in this laboratory that Loir made the chicken cholera virus.

  In a preliminary experiment, Loir also offered the food to native birds and poultry. Rabbits that ate the food died, but not rabbits that avoided it, whereas every test bird died. The rabbit commission refused to award Pasteur the prize. It is just as well his proposal was rejected: one man-made ecological disaster was already one too many.

  Soon after Loir’s arrival in Australia, Arthur Devlin, a grazier, contacted the Pasteur Mission to report that his properties were being affected by a sheep disease referred to locally as ‘Cumberland disease’. Realising that the disease was anthrax, Loir carried out a field trial at Junee Junction in country New Sout
h Wales, similar to Pasteur’s Pouilly-le-Fort trial. A local board was appointed; its chairman, in a wonderful case of nominative determinism, was a sheep grazier called John de Villiers Lamb.

  The vaccine trial was carried out on 39 sheep and six cows. Vaccinated sheep were shorn for identification. Every vaccinated sheep and cow survived. All the unvaccinated sheep and one unvaccinated cow died. Pasteur was asked to supply anthrax vaccine for the whole colony. He said he would arrange it, but when his bid for rabbit eradication was rejected he had a fit of pique and changed his mind. Eventually he was persuaded by a sizeable financial inducement to set up a laboratory in Australia to manufacture anthrax vaccine. This finally led to the manufacture of anthrax vaccine at a new establishment, the McGarvie Smith Institute.

  (Loir was not averse to more scandalous experimentation. In 1891, the most famous and controversial personality of the day, French actor Sarah Bernhardt, arrived in Australia for a tour. She brought two dogs and, just as would happen to Johnny Depp and Amber Heard with their two dogs in 2017, fell foul of Australian quarantine regulations. Loir, a smitten fan, persuaded health authorities to quarantine Sarah Bernhardt’s dogs on Rodd Island. Sarah Bernhardt, who had a penchant for younger men, missed her acting engagements in Brisbane while the pair had a short, passionate affair.)

  Pasteur and rabies

  In 1868, aged just 46, Louis Pasteur suffered a stroke, which left him with speech impairment and permanently paralysed down one side. His faithful wife, Marie, nursed him back to physical and psychological strength. Quite extraordinarily, he would carry out all his future work while still paralysed.

  Pasteur had never forgotten the tragic deaths he had witnessed as an eight-year-old in Arbois, after the wolf attacked the village. Forty-odd years later, rabies infection was still a terrible scourge. In London, for example, 29 people died of rabies in early 1877, stimulating the passing of a ‘Rabies Order’ that permitted police officers to dispose of stray dogs by any means possible in order to combat ‘rabies of the streets’.

  Pasteur’s next great project – and perhaps the crowning achievement of his career – would be to develop a rabies vaccine. He was assisted in this work by a young colleague named Emile Roux, a medical doctor as well as a practising physician, bacteriologist and immunologist.

  Pasteur and Roux showed that the organism responsible for rabies could be found in the spinal cord and brain of affected animals. Seeking to create a vaccine, the two men experimented with strips of spinal cord from rabid rabbits and made a fascinating discovery, as Pasteur reported to the French Academy of Sciences in 1885:

  The spinal cords of these animals are rabid throughout their length with a constancy in their virulence. If, taking the greatest possible care to maintain purity, one removes from these cords sections a few centimetres in length, and then suspends them in dry air, virulence slowly reduces until it finally disappears.

  The longer the cord was dried, the less potent it was in causing rabies when injected into test animals. To work out the ideal level of attenuation, Pasteur and Roux injected dogs with cord extracts of gradually increasing potency; then they created a vaccine.

  Rabies vaccine is different from most vaccines, which are usually given well before exposure to the organism in order to protect against it. Because the incubation period of rabies is weeks or even months, it is possible to protect someone bitten by a rabid animal by giving vaccine even quite a long time after the exposure. In July 1885, Pasteur was visited in Paris by three people from the Alsace region of France, Theodore Vone, nine-year-old Joseph Meister and Joseph’s mother. Monsieur Vone’s dog had developed rabies and had attacked poor Joseph, who had been bitten 14 times, so severely he could hardly walk.

  Pasteur was not a medical doctor but was persuaded to try his rabies vaccine on Joseph. Pasteur later wrote: ‘As the death of this child seemed inevitable, I decided, not without deep and severe unease, as one can well imagine, to try on Joseph Meister the procedure which had worked consistently in dogs.’

  Emile Roux gave Joseph a dose of rabies vaccine – the first ever dose given to a human. Joseph was given 12 more injections of vaccine over the following 10 days, and survived.

  A few months later, in October 1885, Pasteur received a letter from the Mayor of Villers-Farlay, a small town near Arbois. The mayor asked if Pasteur could help a brave 15-year-old shepherd, Jean-Baptiste Jupille, who had been bitten while saving the lives of six younger shepherds being attacked by a rabid dog. Pasteur agreed, and Jean-Baptiste took the next train to Paris. Emile Roux immunised him daily with injections of the rabies vaccine.

  On the sixth day of treatment, Pasteur presented a famous paper to the French Academy of Sciences, in which he described young Jean-Baptiste’s courage and the basis for giving him the new rabies vaccine:

  The Academy perhaps cannot hear without emotion the account of the courageous act and great spirit of the young man whom I have begun to treat last Tuesday. He is a 15-year-old villager called Jean-Baptiste Jupille from Villers-Farlay (Jura) who, seeing a large fierce dog acting suspiciously and threatening a group of six of his little friends, all much younger than him, threw himself, armed only with his whip, in front of the animal. The dog seized Jupille by the left hand. Jupille then threw the dog to the ground, held him down, opened his jaws with his right hand in order to free his left hand, not without receiving many new bites, then with the cord of his whip, muzzled him and striking him with his shoes, killed him.

  After innumerable experiments, I have finally found a method that has already proved successful so consistently in so many dogs that I feel confident of its general applicability to all animals and to man himself.

  After hearing this account, one member asked the academy to award Pasteur the national prize for virtue, which seems a bit excessive, even for the French. Although this was not granted, Pasteur’s efforts did not go unrewarded. The academy publicised the news of Pasteur and Roux’s vaccine and it spread rapidly around the world. It is indicative of Pasteur’s international standing and his ego that he took the lion’s share of the credit, even though Roux made enormous contributions to the research. Pasteur and Roux’s rabies vaccine was just the second human vaccine in the world, after Jenner’s smallpox vaccine.

  People bitten by rabid animals travelled to Paris from far and wide asking to be given the vaccine, including a group of Russian peasants who had been severely mauled by a rabid wolf. Their leader knew a single French word: ‘Pasteur’. Pasteur organised for them to receive his vaccine and all but three survived. The Russian Tsar was so impressed that he awarded Pasteur the Diamond Cross of St Anne, and donated the small fortune of 100,000 francs to aid Pasteur’s research.

  Pasteur was now revered in France and worldwide. When he died in 1895, aged 72, his body lay in state on an elaborate bier before being carried along Paris boulevards lined with thousands of grieving citizens. His funeral was attended by the Emperor of France, princes from Greece and Russia, and Lord Joseph Lister, the great pioneer of sterile surgery, whose own work owed so much to Pasteur.

  Emile Roux’s loyalty did not go unrewarded, because despite suffering from chronic lung disease, he co-founded the Pasteur Institute in 1887, worked there for nearly 50 years and became director, after his mentor Emile Duclaux, who himself had succeeded Pasteur. Roux would achieve fame in his own right for his work on the often fatal disease diphtheria (as we shall see in Chapter 6).

  There was a tragic end, however, to the story of Joseph Meister, the first person injected with the rabies vaccine. Meister spent most of his life working as a caretaker at the Pasteur Institute before committing suicide there in 1940, aged 64. One version of the story concerning his suicide is that German troops ordered him to open Pasteur’s tomb. Joseph refused and committed suicide instead. A less romantic and better documented version has it that Meister was racked with guilt at having sent his family away from Paris, as he was convinced they had been killed. In a sad piece of irony, they returned unharmed th
e same day he took his own life.

  Only human

  A thorough analysis of Louis Pasteur’s secret notebooks has shown that the great scientist was sometimes dishonest about the details of his experiments, secretly made use of other people’s work and failed to acknowledge significant contributions from colleagues like Roux. As an example of his dishonesty, Pasteur and Roux wrote that they had been completely successful in protecting 50 dogs against rabies, but Pasteur’s own records later showed he had tested only 11.

  While it is disappointing to hear that a great scientist was not all he pretended to be, Pasteur was by no means the first such case. It is interesting that he was apparently so convinced his theories were correct he was prepared to falsify his data. He presumably felt that inflating numbers was not cheating but exaggeration. Can someone who behaved as unethically as Pasteur sometimes did be considered a truly great scientist? Or are we just being naïve in creating heroes to worship without making due allowance for human frailty?

  However flawed he was, there is no doubting the immense contribution Louis Pasteur has made to human health, the deaths he has prevented and the misery he has averted. His experimental rigour is honoured in the French government-funded Pasteur Institute, a model of scientific and medical research that has been emulated in many European countries, where these institutions are the major centres of scientific research (unlike in North America, where universities have come to dominate research).

  Pasteur has been called the Father of Immunology, and one of his greatest legacies is the crucial role he played in the development of vaccines and the process of immunisation.

  CHAPTER 4

  The end of polio

  It was 1921. Franklin Delano Roosevelt – FDR, as he was fondly known – was 39 years old and a highly promising young politician. His stocks in the Democratic Party were rising and he had the whole world before him. However, on the fateful day of 10 August all that would change.