Smallpox, Syphilis and Salvation

by Sheryl Persson

  The year after Ethel’s death, on 6 June 1967, Howard Florey and Margaret Jennings married in London. Those who knew them, like Gus Fraenkel, believe that Florey had found happiness late in life.[64] A discreet affair between the two during the early Oxford years had not been as secretive as they thought. After the war in 1946 Margaret and her first husband divorced but she continued to work with Florey for another two decades, publishing over 30 joint scientific papers with Florey and other authors. Sadly, the marriage was very short. Florey was in a very poor state of health and the couple had just over a year together before he died of a heart attack at the age of 69. After Lord Florey’s death in 1968 Lady Margaret Florey remained at the family home in Old Marston, until she passed away in 1994.

  And what of Norman Heatley? He had devised the improved extraction process, designed the ceramic vessels that facilitated the successful production of penicillin and his work in the United States was invaluable in ensuring penicillin was manufactured on an industrial scale. By the end of the war other countries were beginning to produce penicillin. Florey’s own country, Australia, was the first to make the drug available for civilian use. Norman Heatley did not share the 1945 Nobel Prize nor did he receive a knighthood. Finally, in 1978, when Heatley retired from Oxford University, he was honoured with an Order of the British Empire.

  Patience had always been one of Heatley’s virtues. In 1990, on the 50th anniversary of the Oxford team’s success in producing penicillin, the University of Oxford bestowed on Norman Heatley the first honorary Doctor of Medicine degree in its 800-year history. Heatley was still living in the same country cottage that he and his wife, Mercy, bought in 1948 in Old Marston and where they had raised their family. As one would expect he accepted the belated honour humbly: ‘This is an enormous privilege since I am not medically qualified ... I was a third-rate scientist whose only merit was to be in the right place at the right time.’[65] Norman Heatley died on 5 January 2004.

  ***

  No matter who received the credit for penicillin, the metamorphosis of penicillin from Alexander Fleming’s observation of an ‘interesting’ mould into a life-saving drug could not have happened without the systematic, detailed work done by the Oxford team under the leadership of the unusual, urbane and circumspect Howard Florey. He recognised the potential of penicillin, something which Alexander Fleming had failed to do, during the violence and carnage of World War II. As Pasteur had said, humans were always finding new and barbaric means of destruction while, at the same time, evolving new ways for delivering humanity from the scourge of disease.

  Sixty years on the story of the Oxford team remains a fascinating one and their collective achievements have made the world a better and healthier place. But even as penicillin was being hailed as ‘the miracle drug’ in the 1950s, reports began trickling in of patients failing to respond to treatment, of allergic reactions and improper use. In 1946 Alexander Fleming wrote, somewhat scathingly, that if the time came when patients could indulge in self-medication by buying penicillin over the counter and large enough doses were not administered, then the microbes would not be killed and there would be a danger that they would be educated to resist penicillin, resulting in the development of resistant strains of bacteria.[66] It was a bleak but incisive prophecy.

  Despite the early, galloping success of penicillin, as Fleming predicted several strains of bacteria became resistant to penicillin after a few years through mutation. Resistant bacteria multiply when non-resistant bacteria die. To overcome this problem, scientists in the 1950s made artificial penicillin by chemically changing natural penicillin.[67] In recent years ever more powerful antibiotics have been produced to fight an increasingly broad spectrum of microbes and they have been provided to billions of people worldwide.

  It is hard for us nowadays to imagine the world before antibiotics. However, the overuse of antibiotics has continued, creating a frightening new phenomenon: the adaptation through natural selection of genes for resistance to antibiotics by virtually every bacterial pathogen. Hospitals are particularly vulnerable to a new onslaught from these antibiotic-resistant bacteria. More than 70 per cent of bacteria that cause hospital-acquired infections are resistant to at least one of the drugs used to treat them.[68]

  The microbes are fighting back.

  POSTSCRIPT

  A woman named Emma Burkervisc was in a German refugee camp after World War II when her life was saved by a new drug called penicillin. Like many displaced people Emma migrated to Australia as a refugee. Years later she had a job as the tea lady at the Australian National University’s John Curtin School of Medical Research, which Howard Florey had helped to establish. One day on her rounds of the university, Emma bumped into a man who was striding through the corridor. Emma was overcome when she realised that she had come face to face with a legend. The man was Howard Florey, the genius who made penicillin possible, the benefactor who had saved her life and millions more.

  CHAPTER 9

  THE MARCH AGAINST POLIO

  JONAS SALK, ALBERT SABIN AND THE RACE TO MAKE A VACCINE

  As a child I was not interested in science. I was merely interested in things human, the human side of nature if you like, and I continue to be interested in that. That’s what motivates me.[1] Jonas Salk

  It is unusual for a vaccine to take the name of its inventor but in the case of the Salk vaccine, this probably reflects the iconic status of Jonas Salk—and also hints at why controversy courted him. Because of the monumental nature of his achievement, the discovery of a vaccine for polio, Jonas Salk was hailed as the new Pasteur. His is one of the greatest medical success stories of the twentieth century. History does tend to repeat itself, however, and so it is not surprising that Salk’s fame laid him open to attack by his colleagues in the biomedical sciences. Nor is it surprising that his achievements were immediately denigrated and disputed. The sometimes vicious nature of the campaign that was mounted against him revealed the petty side of ‘things human’, in particular the capriciousness of human nature.

  Poliomyelitis has its own modus operandi. Unlike other viral diseases such as smallpox, yellow fever and influenza, polio did not occur in epidemic proportions until relatively recent times, the late nineteenth century. It was an unpredictable and puzzling enemy that seemed to strike out of nowhere and, like diphtheria, many of its victims were children. In the first half of the twentieth century polio epidemics hit many nations and the United States suffered particularly badly. Although polio never killed with the ferocity of other epidemic diseases like smallpox and bubonic plague, it engendered a unique terror. The poliomyelitis epidemics of the 1940s and 1950s inspired dread and panic. Known as infantile paralysis, polio conjured images of children sitting in wheelchairs, walking on crutches and wearing metal leg braces that looked like torture implements from mediaeval times.

  The pursuit of a vaccine to eradicate polio is the stuff of legend, complete with presidents, heroes, archrivals, claims and counterclaims, vilification and disappointments. Fuelling it all was a frightening disease that took the lives of countless children and left many others paralysed, crippled or condemned to life in an iron lung. The competition to be first with a cure created animosity between two men who both had the same goal but who espoused different ways of achieving it. Dr Jonas Salk and Dr Albert Sabin became the public faces of two opposing schools of thought on vaccination and became locked in a battle of their own in the race to find a cure for polio.

  ***

  The word ‘poliomyelitis’ was formed from two Greek words— polios, meaning ‘grey’, myelos, meaning ‘marrow’—and the English suffix ‘itis’, meaning ‘inflammation’ and together they describe the disease. Polio, as it is more commonly called, causes an inflammation of the ‘grey matter’ of the spinal cord.[2] Like many other diseases, it has its own list of aliases. Apart from infantile paralysis, it has also been known as Heine-Medin’s Disease and spinal paralytic paralysis.

  Poliomyelitis is extremely infectiou
s. Spread through human-to-human contact, it usually enters the body through the mouth due to faecally contaminated water or food. The poliovirus is a small ribonucleic acid (RNA) virus. There are three separate strains or immunologic types of the disease: Type I (Brünhilde), Type II (Lansing) and Type III (Leon). The Brünhilde strain was named after a laboratory chimpanzee when this type of polio was isolated in the chimp’s spinal cord. Type II was recovered from the brain and spinal cord of a young boy from Lansing in Michigan, and the third strain was recovered from an eleven-year-old boy named Leon.[3]

  After entering the body and infecting the intestinal wall the virus makes its way through the blood stream to the central nervous system causing muscle weakness and often paralysis. The onset of paralysis can be frighteningly rapid, occurring within a matter of hours—a moment once feared by hundreds of thousands of families. The incubation period can range from three to 35 days, which means that polio can spread widely and take hold in a community before an outbreak becomes apparent. Most people who are infected initially have no symptoms and are unaware that they have been infected; they can pass the disease on through poor hygiene. In all forms of polio, the early symptoms are fatigue, fever, vomiting, headache and pain in the neck and extremities. Although polio can strike a person at any age, over 50 per cent of cases occur in children between the ages of three and five.

  Polio is as tenacious as other scourges that seem determined to survive despite humanity’s best efforts to expunge them from the Earth. Egyptian paintings and carvings dated between 1580 and 1350BC depict young people with withered limbs walking with canes, the cause of which may have been polio. The Roman Emperor Claudius, who walked with a limp, may have been stricken with polio as a child. Medical historians have pointed to the Bible and other early writings in which there are many descriptions of lame and crippled children and of healthy children suddenly becoming paralysed.[4] Polio may very well have been the culprit in some of these cases.

  The nature of polio began to be understood in the late eighteenth century. After numerous outbreaks of a disease that caused ‘debility of the lower extremities’, a British physician, Michael Underwood, wrote the first clinical description. In 1840 a German physician, Jakob Heine, published a medical report which not only described the clinical features of polio but also noted that its symptoms suggested the involvement of the spinal cord. Yet the limited medical knowledge pre-Pasteur’s Germ Theory of Disease, and the fact that the virus escaped detection under the microscopes of the time, meant that Heine and others could not understand polio’s contagious nature. Even with the relatively large outbreaks of polio in Europe during the second half of the nineteenth century, physicians suggested stomach upset, trauma, teething, overheating and chilling as causes, which in the light of what we now know is ludicrous.[5]

  In 1885 the German neurologist Ernst von Strümpell described a cerebral form of poliomyelitis and it was given the name Strümpell’s disease II. The Swedish physician Oskar Karl Medin’s study of poliomyelitis in 1890 led to an understanding of its epidemic character. Dr Ivar Wickman, a pupil of Medin’s, was the first to conclude that polio was transmitted person to person, a realisation he came to because of his experience during the great Swedish epidemic of 1905.[6] It was Oskar Medin and Jacob Heine’s names that were joined in polio’s alias Heine-Medin’s disease.

  The actual poliovirus was identified by Karl Landsteiner in 1908. When the Austrian-born American physician became director of the laboratories of the Royal-Imperial Wilhelmina Hospital in Vienna he began an intensive study of poliomyelitis. One day in 1908 the body of a young polio victim was brought in for autopsy and Landsteiner, assisted by the German pathologist Erwin Popper, began a series of experiments. They injected matter from the brain and spinal cord of the dead child into the abdomens of two rabbits, two guinea pigs, two mice and two different species of monkey. On the sixth day following the injections one of the monkeys was ill, showing signs of paralysis similar to that in poliomyelitis patients.[7] It died two days later but the other animals remained well.

  When Landsteiner and Popper examined the monkey’s central nervous system it appeared similar to that of humans who had died from the disease. Landsteiner could not prove the presence of bacteria in the spinal cord of the child and so concluded that a so-called invisible virus or a virus belonging to the class of protozoa causes the disease. He then transmitted the disease from monkey to monkey and eventually it was possible to transfer a strain of the virus to a rat and a mouse. Thus both the existence and the virulence of the poliovirus were established. In a German publication in 1909 Landsteiner and Popper reported that they had found what they believed to be the cause of the polio epidemics. In the same year, American physician Simon Flexner also successfully induced polio infection in monkeys.

  The pace of research was picking up and with each breakthrough came heightened optimism about a cure for polio. However, by 1913 as epidemics burgeoned in Europe and America they were accompanied by a realisation that a cure was not really on the horizon. From 1900 onwards the cycle of epidemics worldwide became more frequent and destructive. In a major outbreak of polio in the United States in 1916 the government reported over 27,000 cases with 6000 deaths nationally. In New York alone there were 8928 cases and 2407 deaths.[8] In desperation all the authorities could do was to implement quarantine measures which proved utterly ineffective in containing the rampant spread of the disease.

  As polio cut a swathe through more and more countries during the 1920s, afflicting more and more people and leaving many debilitated and unable to breathe, the infamous ‘iron lung’ was developed. This piece of medical equipment, which aided respiration, looked like a metal coffin. Polio patients who needed an iron lung as a substitute for their own lungs spent a large part of the rest of their lives imprisoned in it, lying on their backs, immobile. But there was no choice. Hospital wards filled with rows of these massive machines from which tiny heads protruded were the cause of great despair and a further impetus to find a cure.

  During the 1920s much of the research into polio focused on what was called convalescent serum, which was made from the blood of monkeys and humans who had recently recovered from polio. Some physicians were convinced that injections of the serum could prevent paralysis, as a similar approach had apparently been successful in treating meningitis. Even serum from horses that had been ‘hyperimmunised’ (repeatedly injected with convalescent serum in order to increase their immunity) was tried.[9] This harkened back to the work of Emil von Behring and his Blood Serum Therapy for diphtheria and tetanus. As had been the case with variolation in Edward Jenner’s day, many physicians, including some from the established medical hierarchy, promoted the value of convalescent serum despite the parlous evidence to support it. In the 1930s several reliable field trials indicated that convalescent serum was neither beneficial nor harmful and after two decades it fell out of favour. Hope of an imminent cure for polio was dashed again.

  One of polio’s most high-profile victims was struck down in 1921 and, like so many others, was left paralysed from the waist down. Franklin Delano Roosevelt, who had been a US vice-presidential candidate in 1920, was not a typical polio patient by any means. He was 39 years old at the time he became ill and his illness was to have a long-term impact on the attitudes towards and the treatment of people with disabilities. Although there is some debate today about whether FDR, as he was known, was diagnosed correctly, his experience had a profound effect on his outlook and his policies during his four terms in office as president of the United States from 1933 to 1945. The prestige and wealth of the Roosevelt family were also valuable weapons in the fight against polio.

  In a letter he wrote in October 1924, FDR described his symptoms as the disease began to manifest itself:

  I first had a chill which lasted practically all night. The following morning the muscles of the right knee appeared weak and by afternoon I was unable to support my right leg. That evening the left knee began to weaken al
so and by the following morning, I was unable to stand up. This was accompanied by a continuing temperature of 102 [38.8°C], and I felt achy all over. By the end of the day practically all muscles from the chest down were involved. Above the chest the only symptom was a weakening of the two large thumb muscles making it impossible to write. There was no special pain along the spine and no rigidity of the neck.[10]Roosevelt helped found the National Foundation for Infantile Paralysis (NFIP) in 1937, which later became known as the March of Dimes. The aim of the organisation was to support the rehabilitation of victims of paralytic polio and to assist in the discovery of a vaccine. The foundation was directed by FDR’s friend and former law partner Basil O’Connor. President Roosevelt’s premise was that any problem can be solved if people work together. He created a partnership of volunteers and researchers all with the same goal and within seventeen years of taking up the challenge the Salk vaccine had been developed and polio was on the run, a glorious day that FDR would not live to see; he died in 1945 during the last days of World War II.

  Polio began to strike the United States every summer and autumn with increasingly virulent epidemics. In 1946, 35,000 cases were reported. By the early 1950s the summer had become a time of fear and anxiety for many parents; it was the season when children by the thousands became infected with the crippling disease. Panic and dread would escalate, and in medical and scientific circles the search for a cure picked up pace. At this crucial moment Jonas Salk took up the challenge.