But repositories of the virus still exist and it is not inconceivable that the work that took centuries to achieve could easily be undone, unleashing the unthinkable. These concerns plus the September 11 terrorist attacks in the United States in 2001 and the use of anthrax as a biological weapon later that year have led to a renewed interest in smallpox. There are fears that a weaponised smallpox virus may have been developed as well as recombinant strains of smallpox that have increased virulence and infectivity.
In May 1990 the secretary of the Department of Health and Human Services in the United States called on the Soviet Union to jointly determine the DNA sequences of selected strains of variola virus, followed by destruction of the virus stocks in Atlanta and Moscow.[52] The original plan was to destroy virus stocks on 31 December 1993. The history of smallpox should have ended then with the first deliberate elimination of a biological species from our planet, thus ensuring the extinction of the fatal disease. But the virus has gained a number of reprieves. The slow pace of research caused the planned date of destruction to be delayed until 30 June 1995 but it did not take place then either.
The World Health Organization’s executive board again recommended to the 49th World Health Assembly in January 1996 that the last stocks of smallpox virus be destroyed. This was met with counter-proposals to retain 500,000 doses of a smallpox vaccine containing live vaccinia virus, which is closely related to variola virus, and to also keep the Lister Elstree strain of the virus as seed virus stock for future vaccine production. Scientific opposition to the destruction caused a further delay until June 1999.
The two main arguments against destruction of the virus were that it would eliminate the possibility of future studies and that destruction of the virus in the two known repositories (in 1994, Russia without consultation, moved its virus stocks from Moscow to Vector, a former research centre in Koltsovo) may not guarantee complete eradication.[53] The counter-arguments were that escape of the virus from the laboratories would pose a serious health risk because an increasing proportion of the global population lacks immunity to the disease (there is still no effective treatment once smallpox has been contracted), and that the sequence information and the availability of cloned DNA fragments of the full genome of several strains of the virus would allow most genetic questions to be resolved without the use of live virus stocks.
During 1998 and 1999 an intense debate over the destruction of variola virus stocks took place within the United States government. Arguments for retention won the day. The World Health Assembly passed a resolution to retain the stocks stored in the United States and Russia for three more years for the purpose of biodefence research. Again in May 2002, the WHA decided to extend the research program with live variola virus and not destroy the official stocks. The pattern has continued.
Amidst growing concern, in 2005 an international alliance of non-governmental organisations launched the ‘Put Smallpox in the History Books Instead of the Genetic Engineering Lab’ campaign and urged the WHO to carry out their original intention of destroying all virus stocks.[54] At the 59th World Health Assembly in May 2006 the smallpox issue emerged as the most controversial, creating friction between the representatives of various governments. Many developing countries advocated setting yet another firm date for destroying the virus stocks and stricter WHO controls over the remaining stocks and the research. Concerns were also expressed that the WHO Advisory Committee on Variola Virus Research lacked broad representation and suggested it should be independent of the scientists from the United States and Russian laboratories where stocks are held. Considering the previous delays it is not surprising that there was no agreement and no date was set for destruction. The next major review will be in 2010. And the smallpox virus lives on.
***
Thomas Jefferson, the third president of the United States, wrote to Edward Jenner in 1806 to thank him for ‘erasing from the calendar of human afflictions one of its greatest’, assuring Jenner that, ‘Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated.’[55] It is true that one cannot forget what one has not learnt. Whole generations are now growing up unaware of Jenner and the disease whose name sounded doom. Perhaps this is his true legacy, that to not know about smallpox or Jenner means the disease has not returned.
Edward Jenner had great hopes for humanity and his scientific mind would no doubt grapple with the bitter irony that the eradication of smallpox, that thing which he desired most, has created a new vulnerability: the possibility that the virus could be used as a means of bio-warfare and terrorism. Today, few people have an understanding of how protracted and arduous the battle was to vanquish the speckled monster and fewer and fewer people have personal memories of the horror of the disease. Edward Jenner unselfishly gave to the world the first great medical breakthrough and the hope of perpetual salvation from the most terrible minister of death. Paradoxically, the end of the smallpox story is yet to be written.
POSTSCRIPT
In more recent times Edward Jenner has been accused of acting unethically in using James Phipps as a guinea pig in his experiments. These accusations arise, however, because of unfamiliarity with the medical standards of Jenner’s day and interpreting his actions as putting the boy at risk, rather than protecting him. Jenner was a man of great enerosity and he built a cottage for James Phipps, his first vaccination patient. Even more telling is the fact that Jenner personally planted a rose garden for James. We can only surmise as to how James Phipps felt about the gifts that Jenner gave him but James was one of the very few mourners in attendance at the funeral of a man who was better known in his own time for his study of the cuckoo than for his contribution to saving humankind.
CHAPTER 2
ESTABLISHING THE GERM THEORY OF DISEASE
LOUIS PASTEUR—THE FATHER OF MODERN MEDICINE
I beseech you to take interest in these sacred domains so expressively called laboratories. Ask that there be more and that they be adorned for these are the temples of the future, wealth and wellbeing. It is here that humanity will grow, strengthen and improve. Here, humanity will learn to read progress and individual harmony in the works of nature, while humanity’s own works are all too often those of barbarism, fanaticism and destruction.[1] Louis Pasteur
The wonders that the French chemist Louis Pasteur created in his laboratory, his temple, did much to advance the welfare of humankind in his own time and made possible so many of the great medical advances that were to follow. Scientific giants like Louis Pasteur and Edward Jenner laid the foundations of our knowledge of health and disease and made it possible for the state-of-the-art temples of the future to produce even greater wonders.
Although Edward Jenner invented the first vaccine in 1796 and provided the means by which smallpox could be prevented and eventually eradicated, prior to the mid 1880s innumerable diseases could neither be prevented nor cured. So when news spread that a cure had been discovered for rabies, the horrific disease caused by the bite of a rabid animal, it followed that the scientist who discovered the cure, Louis Pasteur, became an instant cause célèbre. He was revered as a saviour and his name became familiar to people not just in his homeland, France, but all over the world.
However, Pasteur’s contribution is by no means limited to the discovery of a cure for human rabies. It marked the culmination of a lifetime of work and a plethora of discoveries, and the legacy of Pasteur’s superior intellect and scientific method continues to facilitate the progress of humanity. Louis Pasteur believed that his research was ‘enchained to an inescapable, forward-moving logic’, that one discovery, one concept, led inexorably to the next. This ethos drove him to an overwhelming breadth of research and accomplishments.
The Germ Theory of Disease is acknowledged by many as Pasteur’s seminal work. His discovery that infectious diseases are caused by microorganisms has been described as the mos
t important in medical history. Diseases could not be defeated as long as the enemy, micro-organisms, remained unknown. With Pasteur’s discovery the study of microbiology began. His discrediting of spontaneous generation, the 2000-year-old belief that life could arise spontaneously in organic material, is also seen as historically significant as it allowed science to progress. Both of these scientific breakthroughs would not have been possible without Pasteur’s earlier groundbreaking work. Indeed, each of Pasteur’s discoveries over a period of half a century, from the 1850s to the 1890s, represents a link in an uninterrupted chain, beginning with his early work on molecular asymmetry and leading to the pinnacle of his achievement, his rabies vaccine.
It would seem that many cures and advances since Pasteur’s time have also been ‘enchained’, in turn leading to the discovery of the principles of acquired immunity and methods of being able to produce it artificially. Pasteur ushered in a revolution in scientific methodology and research and is acknowledged as the founder of modern medicine and the father of microbiology and immunology.
Pasteur believed that the freedom of creative imagination must, by necessity, be subjected to rigorous experimentation. Not unlike the advice John Hunter had given to Edward Jenner, the maxim Pasteur preached to his students was, ‘Do not put forward anything that you cannot prove by experimentation.’[2] Louis Pasteur was a humanist who put himself and science to work to improve the human condition. In so doing, he never hesitated to take issue with the prevailing ideas of his time when he believed them to be false. For this he often suffered at the hands of his critics and detractors. Even so, within his lifetime, Pasteurean theory and method were embraced well beyond French borders.
Genius of this type cannot help but incite envy and Pasteur’s extraordinary discoveries were often met with scepticism, particularly when they seemed to contradict prevailing views. As Pasteur’s fame grew so did professional and personal opposition, which caused anger and frustration for this zealous scientist. Pasteur alienated chemists, naturalists, physicians and surgeons alike. His professional life was marked by endless conflicts that on occasion precipitated breakdowns in his health.
Descriptions of Pasteur by myriad biographers and acquaintances vary. To many, Pasteur appeared cool, aloof and ungracious and was approachable only to people within his inner circle. These traits were suited to his work ethic and scientific rigour but often alienated his contemporaries. Unable to cope with any kind of criticism, the more he was challenged the more inflammatory he became. In return he challenged his opponents to disprove his claims, often causing offence when he scorned what he perceived as ignorance and lack of experimental skill. As Pasteur’s career progressed and his output increased he had an ever-increasing amount to defend.
When Pasteur’s research on fermentation challenged the established chemical theory of the day he won the ire of the arrogant and influential German chemist, Baron Justus von Liebig. Pasteur came into conflict with the naturalist Félix Pouchet, director of the National History Museum in Rouen, over the theory of spontaneous generation, and was embroiled in a bitter quarrel with prominent physicians over the cause of contagion and disease. While experimenting on vaccination for animal and human diseases, Pasteur made enemies of other scientists, anti-vaccinators and anti-vivisectionists. The most scathing criticism came from Robert Koch, a German research physician. The rivalry between these two scientific icons was vitriolic, intense and lifelong.
Those who worked most closely with Pasteur, however, saw him as a humanitarian and a genius who, although fanatical about his causes, attacked falsehoods not individuals. The physician Emile Roux, who was one of Pasteur’s closest associates, believed that Pasteur’s work proved the brilliance of his mind, ‘but one had to live in his house to fully recognise the goodness of his heart’.[3] Paul de Kruif, another contemporary of Pasteur, called him ‘the scientific nonpareil, the microbe-hunting one and only’. Pasteur’s grandson described him as intolerant of adversaries who refused to listen to the truth, but a man who in his private life was ‘the gentlest, most affectionate and sensitive individual’.[4]
What cannot be contested is that Pasteur furthered the work of Edward Jenner, providing convincing evidence for both the theory and practice of vaccination, a link in the chain which would eventually lead to one of the greatest medical breakthroughs of all time: the development of antibiotics. Pasteur’s discovery that most diseases are caused by germs, which seems so fundamental to us today, has made countless subsequent medical breakthroughs and cures possible. It is impossible to calculate how many lives have been saved as a result.
A QUAINT IDEA
It was not Louis Pasteur who first became aware of the world of microorganisms. That such destructive living microscopic creatures existed was acknowledged in ancient times. Around 46BC, the Roman, Marcus Varro, advised that when building a house or a farm, it should be situated at the foot of a wooded hill where it would be exposed to ‘health-giving winds’. Varro warned against building near swamps because creatures too small to be seen with the eye breed there.[5] In his writings he stated that these creatures float through the air and enter the body by the mouth and nose and cause serious disease.
What had been viewed for centuries as a quant idea became credible because of the scientific bent of a Dutch merchant, Antonie van Leeuwenhoek. Born in 1632, van Leeuwenhoek had no formal education but his passion for scientific observation and description took him in an unusual direction. Compound microscopes were first invented in the 1600s but because they had inherent difficulties with lighting and focal length, van Leeuwenhoek decided to construct his own. In his lifetime he made over 500 microscopes, only ten of which have survived. With a magnification of over 200, van Leeuwenhoek was able to enter a mysterious microscopic world.
Antonie van Leeuwenhoek found what he referred to as ‘very little animalcules’ in rain and pond water and in his own bodily fluids and excretions. He wrote descriptions of these micro-organisms and hired an illustrator to draw them. Between 1673 and 1723, van Leeuwenhoek wrote to the Royal Society in England detailing the wonders of his discoveries. The letters contained the first descriptions of an extraordinary cornucopia: bacteria, protozoa, spermatozoa, red blood cells, striations of muscle cells and the lifecycle of a flea. In the plaque scraped from his teeth van Leeuwenhoek observed ‘an unbelievable great company of living animalcules, a-swimming more nimbly than any’ he had seen previously.[6]
In 1677, after examining spermatozoa in the semen of a man suffering from venereal disease, van Leeuwenhoek examined his own semen and for the next 40 years continued investigating the spermatozoa from molluscs, fish, amphibians, birds and mammals. Van Leeuwenhoek concluded that fertilisation occurred when spermatozoa penetrated an egg and he considered this discovery to be one of the most important in his career.
Two centuries before Pasteur established the Germ Theory of Disease, Antonie van Leeuwenhoek’s studies revealed a world where micro-organisms and human cells battled for dominance. His findings raised some doubt about the prevailing scientific notion that life could generate spontaneously. It was a common belief, for example, that weevils spontaneously generated in grain but van Leeuwenhoek’s observation of corn weevils mating helped to disprove this. He also observed and described the lifecycles of other animals once thought to have been spontaneously generated out of materials such as mud and decaying matter.
Ironically, however, although Pasteur proved that germs cause disease, when he developed his vaccine for the fatal disease rabies, the rhabdovirus which causes it could not be seen because microscopes at the time were still not powerful enough.
***
Louis Pasteur was born in the French village of Dole on 27 December 1822. He was the only son of a poorly educated tanner, Jean Pasteur, a veteran of Napoleon’s army. When Louis was still young the family moved to nearby Arbois where he attended primary and secondary schools. During his early education Louis was not an outstanding student but was artistic and at co
llege painted professional portraits—his name can be found in compendia of nineteenth-century artists.[7]
Louis’ father, however, had aspirations for his son other than art. Gradually, as Louis began to show an interest in chemistry and other scientific subjects, Monsieur Pasteur hoped that Louis would undertake an academic career at the college in Arbois. But Louis far exceeded his father’s expectations. In 1840 he gained a Bachelor of Arts degree from the Royal College in Besançon, followed by a Bachelor of Science in 1842. The head of the college recognised Louis’ prodigious ability and suggested that he apply to the Ecole Normale Supérieure in Paris, a prestigious university which had been founded specifically to train outstanding students for academic careers in science and letters. Louis gained entry in 1843, was awarded a Master of Science degree in 1845 and so began his incomparable scientific career.
Pasteur started as a chemist studying the shapes of organic crystals. In 1847, at the age of 26 when he began working for his doctorate, crystallography was emerging as a branch of chemistry. Pasteur worked on molecular asymmetry, bringing together the principles of crystallography, chemistry and optics. From his experiments Pasteur determined that asymmetric molecules were indicative of living or organic processes and therefore always a product of these. This discovery provided Pasteur with the ‘inescapable forward-moving logic’ that would soon lead him to his studies on alcoholic fermentation.[8] Louis was awarded his doctorate and in the following year, 1848, gained recognition when he presented a paper on his findings on asymmetry before the Paris Academy of Sciences.
Smallpox, Syphilis and Salvation Page 5