Smallpox, Syphilis and Salvation

by Sheryl Persson

  In 1885 news got out that Pasteur and Roux had successfully made 40 dogs resistant to rabies by vaccination and the scientific fraternity was abuzz. Pasteur’s name was again on everyone’s lips. Although encouraged by the initial success, Pasteur was afraid to test the vaccine on humans because he was still unable to isolate the rabic microbe. Despite public pressure he insisted that years of additional research were necessary before human trials could begin. Two people did receive the vaccine, however; patients of physicians who were colleagues of Pasteur. Inexplicably, the first patient was discharged from hospital after receiving only one injection and his fate remains unknown. The second patient, a young girl, was in such an advanced stage of rabies that vaccination was too late and she died before the trial got properly under way.

  Then events, as they so often do, took their own turn. On 6 July 1885, three people arrived unexpectedly at Pasteur’s laboratory. Pasteur later related the events of that day in detail to the French Academy of Sciences. The three, he told the academy, were Theodore Vone, a grocer from Meissengot, who had been bitten on the arm on 4 July by his own rabid dog; Joseph Meister, a nine-year-old boy who had been bitten by Vone’s dog on the same morning; and Joseph’s distraught mother. Joseph was unable to walk properly because he had been knocked to the ground by the dog and bitten on the hand, legs and thighs and was covered with saliva and blood. The worst bites had been cauterised with carbolic acid by the town’s doctor. Monsieur Vone had killed his dog but had not been at risk of catching rabies, Pasteur said, because his skin had not been pierced by the dog’s fangs. Joseph’s mother had pleaded with Pasteur to treat her son as he faced certain death.

  The compassionate Pasteur agonised over the ethics of the situation and the risk to Joseph. He was reluctant to use the vaccine even though the prophylactic procedure had been successful in ‘numberless experiments’ over a three-year period and a series of 90 passages of the virus from rabbit to rabbit, at which point the incubation period of the disease was seven days. Using the same method he had made ‘50 dogs of all ages and breeds refractory to rabies’ without a single failure.[32]

  Two of Pasteur’s medical colleagues examined Joseph, confirming that with fourteen wounds it was almost inevitable that Joseph would come down with rabies. Considering the success of Pasteur’s recent experiments they suggested there was only one option. Pasteur said that he decided ‘not without deep and severe unease, as one can well imagine, to try on Joseph Meister the procedure which had consistently worked in dogs’.[33] With nothing to lose, the boy agreed to be a test patient. Pasteur, putting his reputation on the line yet again (it had become a habit), began administering a series of fourteen painful injections of increasingly virulent material, the details of which Pasteur carefully documented in a written report that he later presented to the academy. Despite Pasteur’s greatest fears, one month later Joseph Meister was healthy, symptom-free and had earned a unique place in history. He was the first person ever to be cured of rabies. Pasteur concluded that Joseph Meister had ‘thus escaped, not only from rabies that his bites would have produced, but also from that which I had inoculated him with in order to check his immunity produced by the treatment, a rabies more virulent than that of ordinary canine rabies’.[34]

  A few months later a young shepherd, Jean-Baptiste Jupille, who had also been bitten by a mad dog, made his way to Pasteur’s door and another trial began. It was during the course of this treatment on 26 October 1885 that Pasteur reported to the French Academy of Sciences on the successful treatment of Joseph Meister and his progress with Jupille. He told of ‘the courageous act and the great spirit of the young man which I have begun to treat last Tuesday’.[35] Pasteur related how the fifteen-year-old Jupille had thrown himself between a group of six much younger children and a rabid dog. When the dog seized him by the left hand, Jupille had wrested the dog to the ground, opened its jaws with his right hand to free his left, and then muzzled the dog with the cord of his whip. Without receiving too many more bites Jupille had managed to kill the dog by striking it with his shoes. Pasteur’s vaccine ultimately saved Jupille as it had saved Joseph.

  The speech that Pasteur delivered was startling in its implications for the treatment of the dreaded disease and did much to ensure Louis Pasteur’s exalted position in the annals of science and medicine. After the success of the vaccine was reported worldwide, victims of dog and wolf bites from as far a field as the United States flocked to Pasteur’s laboratory hoping to be spared an agonising and certain death. The acclaim for Pasteur, saviour and hero both, knew no bounds. His name was soon to become legendary and his cure for rabies raised hope that cures for other infectious diseases such as typhoid, bubonic plague, cholera, diphtheria and syphilis were imminent.

  No matter how great his achievements, Pasteur was never allowed to enjoy his moment of triumph. The old rivals still had not finished with him. When Pasteur published his results on rabies vaccination, there was immediate opposition from Robert Koch. As Pasteur had anticipated Koch accused Pasteur of failing to find the rabies microbe and therefore the ‘methods followed by Pasteur must be called full of mistakes and cannot lead to successful results because they lack microscopic examinations, involve use of impure substances and use unsuitable experimental animals’.[36] Koch ridiculed French microbiology and voiced scathing doubts about the purity of the rabies vaccine. Not content with that, Koch also attacked the way in which Pasteur published his results, accusing Pasteur of withholding unfavourable findings even when they were important to the outcome of the experiment. This is a criticism that has also been levelled at Pasteur in more recent times.

  Pasteur’s response was characteristic, devising experiments that countered one objection after another. On 1 March 1886, Pasteur reported on the progress of his rabies treatments to the Academy of Sciences and called for the creation of a rabies vaccine centre. The now famous Pasteur Institute was established in Paris initially to treat the victims of rabies who were coming to Pasteur’s laboratory in increasing numbers. However, in accordance with Pasteur’s wishes, the institute was soon to become a research facility for infectious diseases and also a teaching centre. Funding to build the institute came from government grants, public subscriptions both local and international, (including 100,000 francs from the Russian Czar expressing his gratitude for curing his subjects who had been infected with rabies) and the income from the rabies vaccine.[37] Although it was a private institute, it had government approval and was inaugurated in 1888 by the French president.

  Louis Pasteur directed the institute that bore his name for the last eight years of his life despite suffering heart problems, no doubt exacerbated by the perpetual stresses of his life. As Pasteur’s health deteriorated his rabies vaccine was restoring health to thousands of victims worldwide, ongoing proof of the significance of Pasteur’s work. Pasteur’s disciples, many of whom later created medical miracles of their own, began to set up a vast international network that still bears Pasteur’s name. In 1891, the first Foreign Institut Pasteur was founded in Vietnam. It must have been of some consolation to Pasteur when his archrival, Robert Koch, finally acknowledged that the rabies vaccine was a success when he set up a rabies vaccination service using Pasteur’s method at the Berlin Hygiene Institute.

  In his latter years Pasteur was honoured throughout the world with prestigious decorations and awards. On 22 December 1892 prominent international scientists gathered to pay homage to the incomparable Pasteur at his 70th birthday jubilee. He received a standing ovation from hundreds of academics, doctors and members of scientific societies. Joseph Lister, a true believer who had applied Pasteur’s Germ Theory of Disease to antiseptics in hospitals, praised Pasteur for having lifted the veil that had hidden infectious diseases for centuries. The two men embraced on stage to thunderous applause. Too overcome to speak, Pasteur allowed his son to deliver his humble address.

  You delegates of foreign countries, who have come a long way to show your sympathy for France, have
given me the greatest joy a man can feel who believes that Science and Peace will prevail over Ignorance and War, that the nations will learn to understand each other, not for destruction but for advancement, and that the future belongs to those who have done most for suffering mankind.[38]Robert Koch failed to attend the jubilee and personal reasons have been suggested for his non-attendance, rather than petty ones. (Ten years after Pasteur’s death, however, Koch made a public visit to the Pasteur Institute in Paris where he received a more than enthusiastic welcome. According to Elie Metchnikov, Robert Koch, Pasteur’s nemesis, returned to the institute later and privately visited Louis Pasteur’s crypt.)

  As director of his own institute, Pasteur turned his attention to developing a vaccine for typhoid, the disease that had killed two of his beloved daughters. But the master scientist would connect no more links in the chain. His failing health and the paralysis of his left side made working in the laboratory increasingly difficult. Pasteur’s grandson’s assertion that his health had been ‘undermined by a life overcharged with ideas, emotions, work, and struggles’ cannot be denied.[39] After suffering two more debilitating strokes, Louis Pasteur died on 28 September 1895, while holding the hand of his beloved wife.

  Louis Pasteur was buried as a national hero by the French government. His funeral was attended by thousands of people, many of whom lined the Parisian boulevards to see his funeral cortege pass by. In England, the London Illustrated News published a full-page portrait of Pasteur on its front page. His remains, initially interred in Nôtre Dame Cathedral, were later transferred to a marble and mosaic crypt in the lower level of the Pasteur Institute.

  ***

  Louis Pasteur was a man of contradictions—a modest man, a humanitarian who referred to himself as ‘a mere chemist’ and, conversely, an intractable, single-minded scientist devoted to his work and incapable of considering opposing opinions. Forced to defend his work at every turn, he withstood hardship, illness and character assassination and endured criticism decade after decade from those who considered him a ‘crackpot’, a ‘charlatan’, or just ‘lucky’. However, Pasteur’s brilliant mind, his tenacity and his belief that science should be used for the public good opened a door to a new understanding of infectious micro-organisms, immunisation and the body’s amazing immune system. Because of the legacy of Louis Pasteur—immunisation, Germ Theory and attenuation—scientists today can target the genes that code for genetic diseases and are working to find molecular ‘magic bullets’ that can inhibit the toxins that germs produce.

  Throughout his working life Pasteur demonstrated the importance of formulating hypotheses and of testing them through controlled experiments. A maxim he quoted often was: ‘It is the worst aberration of the mind to believe things because one wishes them to be so.’ Ironically Pasteur’s detractors accused him of exactly this, of mere speculation that could not be tested. In a book, The Private Science of Louis Pasteur written in 1996, Gerald L. Geison makes similar claims to Pasteur’s contemporaries: that there are discrepancies in Pasteur’s science; in the vernacular—he fudged the results. Geison drew his conclusions from 102 of Pasteur’s laboratory notebooks which had not been available before the 1990s and ignited a new and heated scholarly debate about the validity of Pasteur’s scientific method. Other scholars in their turn now dispute Geison’s findings, accusing him of the same selectivity that he accuses Pasteur of.[40] Claim and counterclaim seem part of a long tradition within the scientific world.

  The more accepted view of Pasteur is that he embodied integrity and altruism. He used science to improve the lot of all he could, whether French provincial farmers whose livelihoods were threatened by anthrax or the desperate, afflicted with rabies, who as a last hope came to his laboratory seeking salvation. Because of Louis Pasteur, rabies is now a vaccine-preventable disease in both humans and animals. If people die from rabies today it is usually because they have not received adequate pre- or post-exposure treatment.

  Although rabies has practically disappeared in most developed countries due to the vaccination of both humans and animals, it would sadden Pasteur to know that it continues to be a major public health problem in some parts of the world. Rabies is, in fact, the tenth most common fatal infectious disease worldwide. The World Health Organization now refers to rabies as a neglected disease.[41] On average, 55,000 human deaths from rabies are reported annually around the world, with more than 99 per cent of these occurring in Africa, Asia and South America. Most cases are caused by rabid dog bites. Of those fatalities approximately 50 per cent, or around 27,000, are children under fifteen years of age. Four million people annually in over 80 countries in which rabies is present require treatment following exposure.

  Pasteur’s original vaccine has been improved. In 1967 the human diploid cell rabies vaccine (HDCV) was introduced and by the end of 2006 it had been given to more than 1.5 million people worldwide. Vaccination remains the sole effective treatment against rabies. Currently pre-exposure immunisation is used to control rabies in domesticated and wild animal populations and given to humans in high-risk jobs such as veterinary surgeons, laboratory personnel, stable hands and foresters. Treatment after exposure is highly successful in preventing the disease if administered within fourteen days of infection. The vaccine overtakes the virus during the incubation period and neutralises it before it reaches the brain and becomes fatal.

  In the United States the number of human rabies deaths is very low compared with the rest of the world. Over the last few decades more and more areas of Europe have been successfully freed from rabies but as international travel and animal importation has increased, so has the incidence of the disease. In the first quarter of 2006 in Europe, there were only two reported cases of rabies in humans and these were in the Russian Federation, but there were 173 reported cases of rabies in wildlife and 241 in domestic animals.[42]

  In developing nations rabies continues to be a serious health issue because of large dog populations that have not been vaccinated. In China, rabies—which is called ‘mad dog disease’—is the country’s second-deadliest pathogen after tuberculosis. The number of cases has risen steadily in recent years because of a rise in pet ownership and a low 3 per cent vaccination rate. In 2006 after an outbreak of rabies in Shandong province, officials ordered the destruction of all dogs within a 5-kilometre radius of the outbreak. In a second cull in Yunnan province, 50,000 dogs were clubbed, electrocuted and buried alive sparking condemnation by the World Health Organization, which promotes humane methods of dog population management.[43]

  In May 2007 an international conference, ‘Towards the Elimination of Rabies in Eurasia’, was held in Paris. It was attended by the World Organization for Animal Health, the World Health Organization, the European Commission and the three WHO-collaborating Centres for Rabies in Europe. It was agreed at the conference that the key to eliminating rabies remains preventing it, and eliminating it from animal populations. To raise awareness of the disease delegates supported the initiative to declare 8 September as World Rabies Day. The commitment was made to continue the battle against rabies with the only weapon available, the vaccine that was the product of Louis Pasteur’s genius, a vaccine for both prevention and cure.

  POSTSCRIPT

  There is a tragic yet heroic end to Joseph Meister’s story. As an adult Joseph was employed at the Pasteur Institute and served for many years as the gatekeeper. In 1940, during World War II, 45 years after his treatment for rabies made medical history, he was ordered by the Nazis, who were occupying Paris, to open Pasteur’s crypt. Joseph Meister chose to commit suicide, shooting himself with his World War I service revolver, rather than allow the resting place of Louis Pasteur to be desecrated. The bond between the boy and the scientist had never been broken. Pasteur had given Joseph the gift of a long life and Joseph chose the time of its end to honour his saviour.

  CHAPTER 3

  OUTWITTING THE ‘WHITE PLAGUE’

  THE CHALLENGE TO CURE TUBERCULOSIS

&nbs
p; I was highly motivated to find antibiotics that could be used to treat gram-negative infections because I had seen soldiers die of such infections. I was also highly motivated to find an antibiotic that could be used to treat tuberculosis because when I was a boy in Passaic, New Jersey, in the 1920s, I had seen neighbors die of TB. We then called it ‘consumption’ because the disease literally consumed them. I knew people who coughed, and wasted away as they lost weight and died.[1] Albert Schatz

  History testifies that cures for the major diseases that afflict humankind do not come easily. Often, what is needed more than skill, ingenuity, knowledge and intelligence are endless patience, commitment and years of repetitive and painstaking work and sometimes sacrifice on the part of many individuals. This was certainly the case, and continues to be so, in the long battle to combat tuberculosis (TB). In the last half of the twentieth century memories of the dreaded lung disease that robbed millions of their lives began to fade due to the discovery of a preventive vaccine and powerful antibiotics. A cautionary note, however: any declaration of victory is premature.

  The continuing saga of finding a cure for TB is not without its own subtext of struggles, rivalries and tragedy and it began with the work of Louis Pasteur’s archrival Robert Koch in 1882 in Berlin. The next episode was written by the French physician and bacteriologist, Albert Calmette, and his veterinarian colleague, Camille Guérin, who in the early 1900s laboured for twenty years to produce the first effective prophylactic vaccine. An ending was in sight when penicillin was developed during World War II but hopes that it would annihilate TB were soon dashed and the hunt was on for more powerful ‘antibiotics’. The plot took a new turn in 1946 when the American biochemists Selman Waksman and Albert Schatz at Rutgers University developed streptomycin, the world’s first broad-spectrum antibiotic. It seemed entirely feasible that tuberculosis, like smallpox, would be eliminated but it is a very determined survivor.