by Sean Martin
Advances in microscopy in the nineteenth century meant that doctors could see evidence of cancer, other than tumours visible to the naked eye. Starting in the late 1820s, the microscope enthusiast Joseph Lister (1786–1869, father of the Lister of antiseptic surgery fame) made improvements to the instrument, principally by having better lenses ground that reduced the amount of optical aberration. With better optics, it became possible to detect the abnormal cells that are cancer’s hallmark. Within a few years of Lister’s improvements, Thomas Hodgkin (1798–1866) described cancer of the lymph nodes (Hodgkin’s lymphoma), using one of Lister’s new microscopes. Lister got himself elected to the Royal Society for his work, and histology took a huge step forward. Just as the discovery of the lymphatic system in the seventeenth century had helped end the humoural theory, so now the new work being done on lymphs helped pave the way for cell theory, which revolutionised our understanding not only of cancer, but also of life itself.
German physician Johannes Peter Müller (1801–1858) built on Hodgkin’s work, theorising that cancer develops when new cells form, while Theodor Schwann (1810–82) and Matthias Jakob Schleiden (1804–81) suggested that cells are fundamental to all life. Schwann and Schleiden’s new cell theory proposed that all living organisms are composed of one or more cells, and that the cell is the most basic unit of life. In 1855, Rudolf Virchow added a third tenet to the theory, that all cells arise only from pre-existing cells (the Latin form, Omnis cellula e cellula, became something of a cell-theoretician’s motto). Virchow suggested that cancer sprang from abnormal cellular changes, having noticed that leukaemia was indicated by the proliferation of white blood cells. No one took Virchow’s theory seriously at the time, but he has since proved to be in essence correct. As we now know, abnormal cell division is the common feature to all forms of cancer.
Research into cancer continued, aided by further advances in technology, such as the discovery of X-rays by Wilhelm Röntgen in 1895, which could detect deeper tumours; of radium by Marie and Pierre Curie in 1898, which could be used in treatment; and the development of another treatment, chemotherapy, by Paul Ehrlich in the first decade of the twentieth century (whose laboratory also developed salvarsan, the first effective modern treatment for syphilis). Some discoveries were accidental. It was found that soldiers who had been the victims of mustard gas attacks in the First World War had significantly lower white blood counts than those who had not, the so-called Krumbhaar effect. Research was conducted at Yale University in the 1940s into nitrogen mustard (the active ingredient of the gas) as a possible cancer treatment. Although it wasn’t used as a prescription treatment, it did assist in the development of new forms of chemotherapy.468 Cancer, of course, was one of the diseases included in the post-war public health drive, and thousands of potential drugs were tested in the 1950s and 60s for potential anti-cancer properties use.
(While no miracle drug for cancer was found, such campaigns can sometimes lead to useful pharmaceutical discoveries, when a drug developed for disease A actually turns out to be effective against disease B. Its subsequent use against disease B is known as repurposing. One such discovery was that thalidomide, while notoriously causing birth defects in babies in the 1960s, has properties that have been successfully used in treatment for leprosy. It is also effective against certain aspects of HIV infection.469)
Scientists are still trying to work out why cancer occurs in the first place. Galen thought people developed the disease due to a melancholy humour, an excess of black bile. Victorian doctors viewed the wearing of corsets with suspicion.470 Later thinkers believed it to be contagious; others, that too much excitement or insufficient exercise was to blame. More recent research suggests that poor diet – especially the diabetesfriendly western kinds – is now thought to account for around one third of all cancers. Processed food, a lack of fruit and vegetables, too much salt and alcohol, are all viewed with the same suspicion that corsets were once subjected to, but with stronger scientific data to back up their possible links to cancer.
Although the list of modern carcinogens is long – more extensive even than anything the Victorians could have thought up – one thing in particular has long been linked to cancer. A paper published as long ago as 1923 highlighted the dangers of smoking, and research conducted in the 1940s found that deaths from lung cancer had gone up exponentially since 1900. Further studies appeared in the 1950s, the era of mass public health initiatives, linking smoking not only to lung cancer, but also to other types of cancer, such as throat, mouth and stomach cancer, and also leukaemia and heart disease.
While doctors were increasingly vocal in their condemnation of smoking, cigarettes were advertised as being good for you, complete with medical endorsement. ‘More doctors smoke Camels than any other cigarette!’ the ads proclaimed. Lucky Strike were advertised as being effective against throat irritation and coughs, and also apparently had weight loss potential (‘To keep a slender figure’); Philip Morris cigarettes were ‘born gentle’, depicting a mother coddling her newborn baby; L&M filters were ‘just what the doctor ordered’. Other brands linked smoking to manliness. Marlboro, after ditching the newborn baby campaign, switched to the rugged Marlboro Man, which became arguably the most iconic of all cigarette campaigns, while Tipalets promised to boost a man’s powers of seduction to almost mesmeric levels: ‘Blow in her face and she’ll follow you anywhere.’
The Marlboro Man was leading a fulfilling life ranching in Idaho, the tobacco companies wanted people to believe. (Perhaps the less said about Tipalets Man, the better.) But from the 1950s tobacco manufacturers knew that cigarettes are addictive and cause cancer, yet spent millions on denial, hiring PR firms, passing the buck and even lying under oath when the matter came up in front of the US Supreme Court. But the truth emerged. As Clive Bates and Andy Rowell note, ‘Thousands of internal tobacco industry documents released through litigation and whistleblowers reveal[ed] the most astonishing systematic corporate deceit of all time.’471 One has to wonder, if corporations can lie for so long about tobacco, what else might they be lying about? But hey, why tell the truth and protect the public’s health, when there’s a lot of money to be made? It’s one of the penalties of an advanced civilisation, after all.
7
New Diseases
Marburg virus
In August 1967, three employees working on vaccines for the pharmaceutical giant Hoechst AG in Marburg, Germany, were taken sick with flu-like symptoms, and were taken to the University Hospital. By the following day, they had enlarged spleens, bloodshot eyes, skin tender to the touch, and ‘sullen, slightly aggressive… behaviour’.472 Other workers from the pharmaceutical plant began to fall ill and, like the original three patients, they had been working on monkey kidney cells. By September, 23 people were very ill, with six more ill in Frankfurt; a third outbreak of the mystery illness occurred in Belgrade. Whatever it was, it was clearly not flu.
Described as agonising, the symptoms of the strange disease progressed from the initial flu-like stage to acute viremia (a physical response to the flood of newly made viruses in the bloodstream): large tender lymph nodes, inflamed spleens, a drop in the number of diseasefighting white blood cells, and a sudden shortage of blood platelets and other factors that are required to stop bleeding. By the sixth day the patients were covered in red rashes, and their skin was too sensitive to be touched. They had raw throats and couldn’t eat, requiring them to be hooked up to intravenous drips. Acute diarrhoea set in by the end of the first week. By the eighth day, microscopic blockages had developed under the skin, giving the patient the appearance of a crimson glow. Red blood cells were immobilised, oxygen not getting through, causing intense pain. By day ten they were vomiting blood. After three weeks of this, the patients’ skins began peeling off as oxygen- and nutrientstarved cells died by the millions. The most intense pain was around the genitals. The disease appeared to be skinning the patients alive at the same time as bleeding them to death. It appeared to have similarities
to acute haemophilia, in that the patients’ blood wasn’t coagulating properly. As one of the Frankfurt doctors noted, ‘Blood is pouring from all apertures’.473
By December 1967, six of the patients were dead. Some had become demented and had fallen into comas from which they never emerged. Two of the patients died of massive heart attacks. Several had permanent liver damage, leaving them with chronic lifelong hepatitis. One became psychotic. Several men became impotent.
The new disease was christened Marburg virus, and was classified as an acute viral haemorrhagic fever. The World Health Organization gave Marburg its highest rating in its risk group categorisation of disease, group 4, which means a disease is highly contagious, and requires the full protective suit to be handled safely. There are no known cures. In other words, Marburg is just about as dangerous as a disease can get; plague is only group 3.
The common factor between the Marburg, Frankfurt and Belgrade outbreaks was that all the victims had been working with monkeys from Uganda, a species of vervet monkey called Cercopithecus aethiops. The animals had been shipped first to Belgrade, and then on to Germany. When the monkeys arrived in Belgrade, 49 of the shipment of 99 were dead. All had died of massive haemorrhages. A week later, the vet who examined them also contracted Marburg. Then his wife, who had looked after him, also fell sick.
With a clear major medical emergency on their hands, a WHO team flew to Uganda to find the source of the monkey virus. Although they found more infected animals, the WHO team could not find where the virus came from. The mystery of Marburg intensified in 1975, when two Australian backpackers contracted the disease in Rhodesia (modern Zimbabwe). The woman survived, but her boyfriend died. No one knew how the man could have contracted it: he initially thought he’d been bitten on the leg by something. He’d slept outdoors in Rhodesia on zebra-grazing land, handled raw meat in Bulawayo, touched monkeys near the Great Zimbabwe ruins, and hand-fed monkeys caged in the lobby of his hotel in Natal. But scientists couldn’t answer the question: how had the man contracted Marburg. And how had it moved from Uganda in 1967 to Rhodesia in 1975?
Lassa fever
In between the two Ugandan and Rhodesian outbreaks of Marburg, another new disease appeared. On 12 January 1969, Laura Wine, a 69-year-old nurse at the Church of the Brethren Mission Hospital in Lassa in eastern Nigeria noticed that she had a bad back. A week later, she also had a sore throat. Penicillin didn’t help. Then she became feverish and severely dehydrated. Her heartbeats became irregular, and she began to suffer from unusual blood-clotting; there was a complete lack of proteins in her urine. On 25 January Wine was flown to a bigger hospital, in the town of Jos. But after a day of convulsions, she died. Then Charlotte Shaw, a nurse who had tended Wine in Lassa, became ill. She also died.
When Wine’s body was autopsied, the doctors ‘gasp[ed] when they saw the devastation; every organ of Shaw’s body was seriously damaged. The heart was stopped up, with loads of blood cells and platelets clogging up the arteries and veins. Fluids and blood filled the lungs. Dead cells and fat droplets clogged the liver and spleen. The kidneys were so congested with dead cells and protein that they had failed to function.’474 There were also no white blood cells in her lymph nodes.
A week later, Lily Pinneo, the assistant at the autopsy, also fell ill. She was transferred first to Lagos, and then to New York City, where she was placed in isolation. Staff in the hospital were afraid of whatever it was Pinneo had; some were ‘highly agitated, some clearly fearful’.475 Her temperature went up to 107° F, her throat filled with lymphatic fluid, and her lungs and chest also filled with fluid. Then Pinneo developed malaria, followed by spasms and convulsions. The disease began attacking her central nervous system. Doctors thought that she had contracted Marburg, but tests proved negative. Then Jordi Casals, the scientist at Yale who was studying the Lassa microbes, also became ill. He had no idea how he had become infected, having followed every safety precaution in the book. Remarkably, the disease seemed to burn itself out in Pinneo, and by May she had recovered. Casals received plasma from Pinneo, and he too recovered.
Jordi Casals continued to research Lassa, although he was now under threat of being closed down. Although his work was potentially lifesaving, the university felt extremely uneasy at the thought of a lethal disease of unknown provenance getting loose in downtown New Haven. As Laurie Garrett notes, Casals was used to these kinds of problems facing the researcher: ‘Ever since he and Karl Johnson had travelled all over the Soviet Union investigating strange haemorrhagic diseases [in the spring of 1965], the pair had discovered that the real danger was not the viruses, but politics.’476 They had been researching Omsk haemorrhagic fever, Crimean-type fever and Central Asian haemorrhagic fever, and the trip proved very useful for all the scientists. But every time Casals and Johnson returned to the US, they were hounded by the CIA, who clearly had an eye on the biological warfare potential of these new diseases.477
With the added pressure of closure and the interest of the CIA, Casals was able to make progress on Lassa. He found that the virus could be spread four ways: by inhaling viral particles, by contact with contaminated urine, through blood to blood contact, ‘or by some less clear method involving laboratory mice.’478 This led Casals to think that the reservoir could be rodents, but he had no proof. And then, somehow, a lab technician, who had not been working with Casals, died of Lassa. It was the excuse the university needed to shut Casals down, and research switched to Level 4 labs at CDC in Atlanta.
The hunt for Lassa’s reservoir continued. There was a serious outbreak in Nigeria in January 1970, when 28 people contracted the disease. Blood serum from Lily Pinneo, which had saved the life of Jordi Casals, was sent but did not get through due to the Biafran war, which was still ongoing at the time. Thirteen died. Scientists managed to get to Sierra Leone in September 1972 when Lassa broke out there. While serum was administered to patients, a large trapping operation was mounted. It was thought that the Lassa reservoir was a common African animal, and so the team set about collecting more than 640 animals, including mice, bats, rats and shrews. One type of common African rat, Mastomys natalensis, tested positive for Lassa. Further analysis revealed that Lassa was spread to humans through its droppings. As the rat was a common visitor to people’s homes, seeking warmth or food, Lassa could potentially be spread easily. And the disease could already be well established. Scientists didn’t know, and waited for the next outbreak.
Ebola
The next major outbreak in Africa was not of Lassa, but of yet another deadly and previously unknown disease, one that would eclipse its two elder siblings. On 28 August 1976, at the Catholic Mission Hospital in Yambuku in northern Zaire (now the Democratic Republic of Congo), a man was admitted, suffering from severe diarrhoea and a nosebleed. The Sisters had no idea who he was, or where he had come from, and were puzzled by his symptoms. After two days, the man discharged himself, and they never saw him again. Another of their patients was a 16-year-old girl, Yombe Ngongo, who was receiving treatment for what appeared to be severe anaemia. Naturally, the nuns didn’t link the girl with the man from the bush. Their health problems seemed entirely different.
And then on 1 September, Mabalo Lokela, the headmaster of the local school, appeared, suffering from what was thought to be malaria. He was given shots of quinine, the antimalarial drug, and went home. Four days later, he was back. This time, he was vomiting and had acute diarrhoea, had pains in his chest, his skin was tight and dry, his eyes sunken by serious dehydration. He was also bleeding from the gums, his nose, and there was blood in his diarrhoea and vomit. The Sisters injected him with further shots, but his condition worsened. They gave him aspirin, nivaquine, blood coagulants, calcium, cardiac stimulants, caffeine, camphor and antibiotics. Nothing worked. Mabalo Lokela died on 8 September. A day earlier, Yombe Ngongo had died in her home village.
And then things began to escalate at the Mission Hospital. Over the next two weeks, 21 people died, all showing similar symptoms to Mab
alo’s. They were suffering from pains in the abdomen and chest; were feverish; had headaches and sore throats; were nauseous and vomited – some were vomiting blood; had diarrhoea but also the inability to pass urine (anuria); joint and muscle pain; general weakness and loss of appetite; had sore, red eyes and suffered from rapid breath. Some developed rashes and suffered from hiccups and experienced a constant ringing in the ears. In addition to the vomiting of blood, some experienced bleeding from the gums and anus. It was not uncommon for patients to go into shock. As Laurie Garrett notes,
The horror was magnified by the behavior of the many patients whose minds seemed to snap. Some tore off their clothing and ran out of the hospital, screaming incoherently. Others cried out to unseen visitors, or stared out of ghost eyes without recognizing wives, husbands, or children at their sides.479
The disease began to spread to the neighbouring villages as terrified patients fled the hospital, taking the disease with them. Huts belonging to dead villagers were burned to the ground in a frantic attempt to stop the disease spreading.
Blood samples were sent to various labs. The one that arrived at the Institute for Tropical Medicine in Antwerp came in a thermos flask. When it was opened, Peter Piot – who was to witness early AIDS cases – recalled, one of the test tubes inside had cracked in transit. Blood was swishing around freely. Piot and his colleagues had no real idea at the time just how much danger they were in. ‘Indeed, the Belgians laboured under conditions no more sophisticated or secure than might be found in a typical high school biology lab… all concerned would later express astonishment that they suffered no ill consequences from such frivolous disregard of the potential hazards of the microbes.’480 Initially suspecting the Yambuku disease to be yellow fever, they performed the necessary tests, but they turned up negative. There was also the possibility that Yambuku was experiencing an outbreak of Marburg, as the symptoms were similar. But when Piot examined blood taken from one of the Sisters, he found something no one had seen before – strange viruses shaped like question marks.
