Smallpox, Syphilis and Salvation

by Sheryl Persson

  Jonas Salk saw scientists falling into two categories, the ‘evolvers’ and the ‘maintainers of the status quo’. According to Salk, when it comes to medical breakthroughs it is the evolvers who cause things to change while the maintainers do everything to stop things changing. The two are different in interpretation, temperament and personality and evolvers are, like Salk, a much rarer species.

  When assessing Jonas Salk’s career two things are certain. He won the race to find an effective vaccine against polio but received few honours for being the first to save generations of children not only from death but, in some cases, as the cliché goes, a fate worse than death. Jonas Salk was awarded a Congressional Medal of Honour in 1955 and the Presidential Medal of Freedom in 1977 but he was not elected to the National Academy of Sciences and did not win a Nobel Prize. Perhaps his standing amongst his peers never recovered but he won the adulation of a grateful world.

  Jonas Salk continued to conduct research and publish books, some in collaboration with his sons who also became medical scientists. In his last years he joined the search for a vaccine for AIDS. Jonas Salk died of congestive heart failure on 23 June 1995, aged 80.

  Basil O’Connor remained a steadfast supporter of Jonas Salk and summed up what he saw as a great injustice. Salk had ‘showed the world how to eliminate paralytic polio’, O’Connor said, ‘and you’d think he had halitosis or had committed a felony’.[49] Nobel laureate Renato Dulbecco, in an obituary he wrote for Salk, expressed the same sentiments with the appropriate gravitas: ‘The fact that a fundamental advance in human health could not be recognised as a scientific contribution raises the question of the role of science in our society.’[50]

  It was Jonas Salk’s firm belief that in the future science should be able to provide a greater understanding of how the mind works, and how we can use our minds to better advantage to improve health by enhancing the positive and reducing the negative. He shared Louis Pasteur’s view of humankind that some people are constructive and others destructive and it is necessary to have enough of the former to overcome the problems of each age. Jonas Salk made a superhuman effort to reduce the negative in the world by finding a cure for polio, one of the greatest problems of his age.

  Albert Sabin went on to play a significant role in the vaccination programs run by the Pan-American Union and the World Health Organization. Sabin was researching the role of viruses in cancer at the time of his death in 1993. He was 86 years old.

  ***

  Authorities in various countries interpreted the risks and benefits of the killed and the attenuated vaccines differently, depending on how successful they had already been in reducing the incidence of polio. In the 1970s, because of its lower cost and long-term efficacy, the World Health Organization included the Sabin vaccine in the packet of subsidised vaccines it provided to poor countries under its immunisation program. In 1974 the WHO launched its Expanded Programme on Immunisation (EPI) because, worldwide, less than 5 per cent of children in the first year of life were immunised against six initial target diseases: diphtheria, tetanus, pertussis, measles, tuberculosis and polio. Extraordinary minds during a period of almost a century had developed vaccines for all of these diseases.

  With approximately 350,000 cases of polio still occurring worldwide in 1988, the World Health Assembly launched the Global Polio Eradication Initiative. During a two-year period, 1995–96, approximately 400 million children under the age of five were immunised against polio, mostly with the Sabin vaccine. By 1998 more than 450 million children had been vaccinated under this scheme and the number of polio cases worldwide had fallen to approximately 7000 in 1999.

  In the United States the oral vaccine is no longer administered particularly because of vaccine-induced paralytic polio. During the 1990s improved vaccines were introduced with variable results. The latest Inactivated Polio Vaccine (IPV) is known to be 90 per cent effective after two doses and 99 per cent effective after three doses. In Australia in 2005 this injectable IPV replaced the oral polio vaccine, again because of the very small risk of vaccine-induced polio. It is now recommended that children receive doses of IPV or IPV combined with the DTaP (diphtheria, tetanus and acellular pertussis).

  The WHO is committed to the same goal as Jonas Salk: ridding the world of polio. The Western Pacific Region and European Region were certified polio free in 2002. By 2003 only 784 cases were reported worldwide. The number of countries where polio remained a chronic problem in 2004 had fallen from 125 to just six: Egypt, Niger, Nigeria, Afghanistan, India and Pakistan.[51] In these countries the WHO works with governments and UNICEF to coordinate immunisation drives. Every six weeks thousands of local health workers and volunteers fan out through cities and villages, each worker carrying a thermos of vaccine vials, maps and clipboards. We are reminded of Franklin Delano Roosevelt’s sentiments that anything can be achieved if everyone is willing to work together.

  The cost of the polio vaccination campaigns is enormous and questions often arise regarding the economic value and sustainability. But in 2004 Dr Bruce Aylward, the coordinator of the WHO’s polio eradication program, noted that the world is like a forest and one case of polio could start a wildfire that might take years to put out.[52]

  On 12 April 2005, the 50th anniversary of Jonas Salk’s vaccine was celebrated but the planet was still not polio free. Polio, like other diseases, could once again become common because the virus that causes it still exists. In fact the Global Polio Eradication Initiative faced an increase in global cases in 2006, the result of an ongoing outbreak in northern Nigeria and a new outbreak in western Uttar Pradesh, India.[53] Most of the cases occurred in Nigeria after immunisation was curtailed in 2002 due to rumours that the program was a Western plot to sterilise Muslim girls. An outbreak of polio in Somalia in July 2005 highlighted the difficulty of wiping out a stubborn global scourge. Two hundred Somali children were left paralysed by the outbreak and by then nineteen countries had been reinfected with polio because of the situation in Nigeria.

  Yemen, Indonesia, Saudi Arabia, Sudan and Iraq have all been re-infected since 2004 causing a threat to the region. Because of the war in Iraq and the breakdown of services and infrastructure in November 2006, a national polio immunisation drive conducted by UNICEF, the second for the year, was launched by the Iraqi Ministry of Health despite security concerns. Iraq’s last polio case was reported in 2000. During April and May 5400 mobile vaccinators travelled house to house across Iraq to immunise every child under the age of five, and over 96 per cent of the target population, almost 5 million children, were immunised.[54]

  The recent global resurgence of the poliovirus has brought a renewed threat to the whole world, making routine immunisation campaigns critical to safeguard all children and ensure they do not suffer the fate that was once visited on so many. Jonas Salk made great personal sacrifices to save the children of his generation and his fervent hope was that children everywhere would be safe from polio forever.

  POSTSCRIPT

  The fearsome-looking iron lung that once filled hospital wards now has a marginal place in medical treatment. It is half a century since vaccination put an end to polio epidemics and modern, much smaller mechanical ventilators that push air into the airway with positive pressure have been developed. One victim of polio who still relies on an iron lung to keep her breathing is an Australian woman, June Middleton. June is something of an anomaly and in February 2007 she was presented with a certificate from the Guinness World Records for a record she would have preferred not to achieve: the longest time spent in an iron lung. At 80 years of age June Middleton has spent eighteen hours a day for the last 57 years of her life inside an artificial lung machine. June contracted polio in 1949 at the age of 23 and since that time two generations of children have been born and most would never have feared poliomyelitis nor would they have heard of an iron lung.

  CHAPTER 10

  TARGETING CHILDHOOD LEUKAEMIA

  GERTRUDE ELION, GEORGE HITCHINGS AND RATIONAL DRUG DES
IGN

  I watched him go over a period of months in a very painful way, and it suddenly occurred to me that what I really needed to do was to become a scientist, and particularly a chemist, so that I would go out there and make a cure for cancer.[1] Gertrude Elion

  My greatest satisfaction has come from knowing that our efforts helped to save lives and relieve suffering. When I was baptised, my father held me up and dedicated my life to the service of mankind. I am very proud that, in some measure, I have been able to fulfill his hopes.[2] Dr George Hitchings

  When Gertrude Elion joined the Wellcome Research Laboratories in New York in 1944 as an assistant to Dr George Hitchings, she was a woman entering what was considered to be a man’s world. Fate brought two brilliant and like minds together. Both had committed their lives to research in order to find cures for diseases such as cancer—diseases that had robbed them of loved ones and that caused great suffering in the world. Both were humanitarians determined to improve the lives of others. Together they developed a range of therapeutic and curative drugs, including the first cure for childhood leukaemia. Here were two dedicated scientists who worked together harmoniously and whose story, for once, is untainted by rivalry, intrigue or scandal; and the story is all the more exceptional because one of them was a woman.

  The scope and importance of the work of Gertrude Elion and George Hitchings is nothing short of astonishing. Probably the greatest legacy resulting from their research was the development of 6-MP, a drug that has provided both treatment and cure for childhood leukaemia. The prospect was very bleak for leukaemia sufferers in the 1950s. Today, most children suffering from leukaemia who are treated with 6-MP, in combination with other drugs, become free of the disease and there is a strong likelihood that it will never recur. Most childhood leukaemias now have very high remission rates with some forms as high as 90 per cent. Because of Gertrude Elion and George Hitchings, for the majority of children suffering from childhood leukaemia today the prognosis is good and a cure is the most likely outcome.

  Leukaemia, which occurs worldwide, is a form of cancer, specifically cancer of the white blood cells (also called leucocytes). Leukaemia represents just over 5 per cent of all types of cancers but for childhood cancers it is closer to 25 per cent.[3] When a child has leukaemia, large numbers of abnormal white blood cells are produced in their bone marrow, crowding it and flooding the bloodstream. As a result the white blood cells cannot perform their proper role of protecting the body against disease because they are defective. As leukaemia progresses, the cancer interferes with the body’s production of other types of blood cells, including red blood cells and platelets and there is an increased risk of infection caused by the abnormalities in the white cells.

  There are different types of childhood leukaemia, which can be classified as acute or chronic. In children, about 98 per cent of leukaemias are acute. This is where it becomes more complicated. Acute childhood leukaemias can then be divided into acute lymphocytic leukaemia (ALL) and acute myelogenous leukaemia (AML), depending on whether the specific white blood cells called lymphocytes are involved. Lymphocytes are critically important because they are linked to the body’s immune defences. Approximately 60 per cent of children with leukaemia have ALL, and about 38 per cent have AML. Children may also have the slow-growing chronic myelogenous leukaemia (CML) but this is very rare.[4]

  The symptoms that children suffer are very distressing. Because the infection-fighting white blood cells are defective, sufferers can experience episodes of fevers and infections and can also become anaemic because leukaemia affects the bone marrow’s production of oxygen-carrying red blood cells. Consequently children with leukaemia become exceptionally vulnerable. They are tired, short of breath, have a poor appetite and they bruise and bleed very easily—leukaemia also destroys the bone marrow’s ability to produce clot-forming platelets. There are a range of other symptoms as well: pain in the bones or joints, swollen lymph nodes in the neck, groin and other parts of the body; and with some leukaemias headaches, seizures, balance problems, abnormal vision and even problems with blood flow to and from the heart all occur.

  As to the cause of leukaemia, the consensus is that a number of factors are involved. It is now known that childhood leukaemia results from abnormal gene function and that an inherited predisposition to leukaemia is a significant factor. The question of genetic susceptibility was studied by Frederick Gunz at Sydney Hospital in Australia in the 1970s.He concluded that evidence from family studies reinforced the theory of a genetic basis in some people, particularly for chronic lymphatic leukaemia. Twin studies have also established a genetic link and siblings of people who have the disease can have up to a four-fold increase in risk.

  It is accepted that ionising radiation can also be a cause. Around three years after the atom bombs were dropped on Hiroshima and Nagasaki in 1945 there was a rise in the incidence of leukaemia. This peaked at around six years and returned to normal incidence twenty years after the bombings. Overall, however, relatively few people were affected compared with the number exposed to radiation, which raised the question of individual susceptibility. Concern about nuclear power causing leukaemia has been highlighted because of clusters of cases reported in areas surrounding nuclear power stations in various parts of the world. Childhood cases appear to be more prominent within these clusters. Again, because relatively small numbers of people are affected individual susceptibility seems a reasonable assumption.

  A major study conducted by the Centre for Clinical Epidemiology at Leeds University in England began in 1984. The centre collects information from patients and their families. In order to understand the processes that can lead to leukaemia and related cancers, information on lifestyle patterns, environmental exposure and genetic make-up is being analysed. Research at the centre has already found that certain exposures can increase the likelihood of a person developing leukaemia. For example, there appears to be an association between smoking and acute leukaemia in adults. Also people with certain genes appear to be at greater risk of developing leukaemia if they are exposed to chemicals such as benzene. The study is ongoing and over time will collect data on millions of people.

  NOT WOMEN’S WORK

  The first great inroads into curing leukaemia were made by George Hitchings and Gertrude Elion, and both seemed destined from an early age to carry out their life-saving work. Gertrude Belle Elion, better known to colleagues, family and friends as Trudy, was born in New York City on 23 January 1918 at the end of World War I. Both of her parents were immigrants, her father having migrated to the United States from Lithuania when he was twelve years old and her mother from Poland at the age of fourteen.[5]

  Gertrude’s father became a successful dentist after graduating from the New York University School of Dentistry in 1914. The family lived in a large apartment in Manhattan adjoining Gertrude’s father’s dental office. Gertrude had one brother who was born when she was six and not long after his birth the family moved to the Bronx. There were open spaces where the children played and the Bronx Zoo was almost in their backyard. In many interviews, Elion spoke about her happy childhood.

  The Elion children attended a public school within walking distance of their house and, even though class sizes were large, Gertrude believed that they received a good basic education. She was a child with an insatiable thirst for knowledge and she excelled at an early age. At twelve Gertrude was accelerated to a class two years ahead of her peers and her junior high school report card from 1930 reflects her abilities in a wide range of subjects. Her one consistently low grade was in Physical Education. Later when she was in college receiving As for all subjects there was still one exception: a C in Physical Education.

  Gertrude was only fifteen when she enrolled at Hunter College. It was the 1930s, a time of economic hardship due to the Great Depression. Gertrude later wrote that she would not have been able to receive a higher education had it not been for good grades that she achieved in high school and the fact that Hunter
College did not charge its students fees, which would have been a tragedy for such a gifted woman.

  The death of Gertrude’s grandfather from stomach cancer shortly before she began her studies at Hunter College had a profound and abiding effect on her. He had followed the family to America from his homeland and was a devoted grandfather, reading to his little granddaughter and taking her on walks. He contributed much to Gertrude’s contented early years. As he lay dying Gertrude spent time with him in the hospital. She later recalled the sad time.

  I watched him go over a period of months in a very painful way, and it suddenly occurred to me that what I really needed to do was to become a scientist, and particularly a chemist, so that I would go out there and make a cure for cancer.[6]It was a defining moment in her life and at the young age of fifteen Gertrude Elion made the selfless decision to devote herself to medicine. As a first step she studied chemistry and by 1937 had completed her Bachelor’s degree. Another tragic event in her young life led Gertrude to renew her commitment. She met and fell in love with a young man and they planned to marry. Not long after her fiancé graduated from university and started his career working for Merrill Lynch he became ill. Then soon after Gertrude’s own graduation from Hunter College, her fiancé died of a bacterial infection, subacute bacterial endocarditis, an inflammation of the heart lining.[7] Two years later when penicillin was discovered, Gertrude realised that the man she loved could have been saved and this tragic event reinforced in her mind the importance of scientific discovery. Gertrude Elion said that it was never her intention not to marry after this loss but she did remain single for the rest of her life. She was not without close family, however, and remained very much a part of her brother’s life even when they were living in different parts of the country. Gertrude was devoted to his children, her four nephews and two nieces.