Wednesday, May 15, 2013

VIRUSES ARE LIKE ZOMBIES

VIRUSES ARE LIKE ZOMBIES: they are not quite dead and, to keep going, they have to feed on living flesh. But they are not quite alive either. When a bacteriologist wants to needle a virologist, she dismisses viruses as “infectious chemicals”, not properly living things. Properly living things are made of cells, membrane-bound bags of vibrant chemical reactions. At best, viruses can be characterised as “minimal biological entities”.

In classical Latin, the word virus was applied to any poisonous secretions or venoms, or metaphorically to anything with a virulent or malignant quality. Cicero uses it this way in his De Amicitia, with his turn of phrase evomat virus acerbitatis suae meaning “spits out the venom of their own bitterness”. In English, the word had started to take on a more modern meaning as "material that causes infectious disease" by the eighteenth century. Edward Jenner in his groundbreaking text from 1798 AN INQUIRY INTO THE CAUSES AND EFFECTS OF THE VARIOLÆ VACCINÆ uses the term “virus” more than twenty times to describe the infectious material that causes cowpox.

Louis Pasteur, one of the founders of medical microbiology, is buried in a neo-Byzantine chapel within the Institut Pasteur at the heart of Paris. The walls of the crypt are lined with exquisite marble, above which sit mosaics providing vignettes from Pasteur’s highly productive life. The penultimate vignette carries the inscription “1880 virus vaccins” and refers to Pasteur’s work on the production of artificial vaccines against chicken cholera and anthrax. The final inscription refers to Pasteur’s work on vaccination against rabies.

Pasteur was puzzled by rabies. He could grow and/or use a microscope to visualise the causative agents of most of the infectious diseases on which he worked—these agents we now call bacteria. But the cause of rabies eluded him—and for good reason, as we now know it was caused by a virus rather than a bacterium. However, one of his staff, Charles Chamberland, laid the groundwork for the discovery of what we now call viruses, by inventing the Chamberland-Pasteur filter. This filter, made from unglazed porcelain, had such a small pore size (less than a millionth of a metre), that it could be used to remove bacteria from a liquid suspension.

In the early days of the new Germ Theory of Infection, it was thought that all infectious agents could be retained by filters and grown on a nutrient medium. However, in the last decade of the nineteenth century, it became clear that some infectious agents did not comply with these expectations. In 1892, Dmitri Ivanowski, working in St Petersburg, used a filter candle on an extract of plants with tobacco mosaic disease and showed that, even after filtration, the extract remained infectious. But he didn’t quite get clear in his head what had happened—he thought perhaps what he was seeing was a toxin produced by a bacterium.

Six years later, the Dutch scientist Martinus Beijerinck described his own similar experiments with infectious bacteria-free extracts of tobacco mosaic disease, but this time made the conceptual leap to the idea of a new kind of infectious agent, which he termed “filterable virus” that would grow only in the presence of living cells. The adjective was soon dropped and modern usage of the term “virus” became widespread.

In 1906, the Italian pathologist, Adelchi Negri showed that Jenner’s vaccine virus was also a “filterable virus” and soon afterwards, the causative agent of smallpox was also shown to be viral in nature.

But what aside from size makes viruses different from bacteria?...

Tuesday, May 14, 2013

The Diagnosis: EAST BIRMINGHAM HOSPITAL, THURSDAY, 24TH AUGUST 1978

The art is long, life is short, opportunity fleeting, experiment dangerous, judgment difficult.
Hippocrates of Cos

Janet’s parents had grown tired of watching over their ailing daughter, as her condition went from bad to worse. They called their own GP, Dr Annis Price, to Myrtle Avenue to see Janet. Dr Price decided things were serious enough for a hospital opinion. He referred Janet Parker to the local infectious disease hospital with a diagnosis of “Rash and Fever”.

Janet made the nine-mile journey to East Birmingham Hospital in an ordinary ambulance. At three o’clock that afternoon she was admitted to a single isolation cubicle in Ward 32. Shortly afterwards, she was seen by the Duty Consultant Physician for the Department of Communicable and Tropical Disease, who that day happened to be Professor Hugh Vivian Morgan.

A quietly spoken Welshman, with deep Christian convictions, Hugh Morgan had been Professor of Medicine at the University of Khartoum in the Sudan from 1952 to 1968. In this role, he had criss-crossed the country in a truck-cum-trailer that acted as a mobile clinic and laboratory, ministering to the medical needs of the local population. His services to medicine and medical education in Africa culminated in the award of a CBE in 1966.

By the time he encountered Janet Parker, Morgan had been in Birmingham for over ten years, his clinical experience overseas and his good grasp of Arabic proving valuable in dealing with immigrants from the Tropics and Middle East. Now sixty-two years old, bald on top, with a wide-domed forehead, a warm friendly smile and an unthreatening avuncular demeanour, Morgan was close to the end of long and distinguished career. His memory was starting to falter—the nurses had already nicknamed him “the absent-minded professor”. Sadly, a few years later, in retirement, his forgetfulness was to be transformed into full-blown Alzheimer’s disease. But on that fateful day in 1978, although he might have started to loose his grip on the superficial trivia of the here-and-now, Morgan was still in full possession of a fine-tuned diagnostic acumen and of a rich treasure trove of clinical experience. Most importantly, from textbook knowledge and from face-to-face encounters in Africa, smallpox was seared deep into his intellect.

“Judgment difficult”, Hippocrates had said. What to do when faced with a difficult diagnosis? There is a saying among medics that “common things occur commonly”. This is applied as a corrective to those who have spent more time with textbooks than with patients, to prevent them jumping straight to the rare small print stuff when making a diagnosis. The three GPs who had seen Janet Parker—all good solid chaps, trained at the Medical School in Birmingham— had obviously been working to this rule. And not unreasonably: a year after it had been eradicated, not just from England’s green and pleasant land, but from the whole planet, smallpox had to rank as the smallest of small print in any differential diagnosis. In fact, it was quite frankly impossible!

Another medical aphorism along similar lines is “when you hear the sound of hooves, think horses, not zebras”. Smallpox, in suburban Birmingham in the summer of 1978, was not even a zebra; it was a unicorn!

But faced with Janet’s signs and symptoms, Morgan was worried. He trusted what his senses and his intellect were telling him—for someone with his tangible experience of the disease, smallpox, however improbable, could not be dismissed as impossible. Yet the quietly spoken veteran of Khartoum was no sensationalist. He was not going to announce triumphantly to the world, or even to his colleagues, that he had single-handedly diagnosed a case of smallpox. Instead, he did what any sensible person would do when confronted with a unicorn in the garden—he performed a sanity check: he sought a second opinion. He turned for advice to Birmingham’s designated smallpox consultant, a scotsman named Alasdair Geddes.

Geddes had held this position since he had returned from a stint working on the eradication campaign in Bangladesh in 1973. In this role, he had been called out half a dozen times in the previous five years to examine suspected cases of smallpox. All so far had turned out to be false alarms: either bad cases of chickenpox or a nasty rash from a condition known as Stevens-Johnson syndrome. Yet each time, he had been paid the princely sum of twenty pounds.

At 7.30pm, the Welshman phoned the Scotsman and asked him to come in and see what he called “a lady with an unusual rash who worked in the east wing of the Medical School”. Morgan might have fleetingly raised the possibility of smallpox, but for him it still didn’t make much sense. You didn’t get unicorns on the lawn in England.

Nirvana in the Laboratory: PAKISTAN, FEBRUARY 1970

Lives of great men all remind us 
We can make our lives sublime 
And departing leave behind us 
Footprints on the sands of time.
A Psalm of Life,
Longfellow

PAKISTAN: A LAND BETWEEN East and West, where the Eurasian and Indian plates collide: the Indus valley, flanked to the west by the Baluchistan plateau and to the north by the foothills of the Himalayas.

Historians may argue over whether great men really do shape history or merely ride its currents. Yet, several great men had clearly left footprints on the sands of time of this landscape. Sometime before 400 BCE, Siddhartha Gautama, established a new religion, Buddhism, which rapidly permeated the region.

In the third century BCE, the Macedonian general, Alexander the Great, swept in from the West, ushering in a new era of Indo-Greek civilization. To the East, the Indian emperor Ashoka, made Buddhism the state religion of a multi-ethnic empire. The resulting fusion of Greek sculpture with Buddhist religious art culminated in the now-familiar statues of the Buddha scattered across the Southern and Eastern Asia. In what is now central Afghanistan, monumental standing Buddhas carved into a cliff face stood for nearly fifteen centuries, before they were destroyed in a fit of intolerance by the Taliban. Buddhism itself lasted a thousand years in Pakistan before, in the eight century of the common era, the region fell under the influence of another great man, Muḥammad ibn ‘Abd Allah, and another religion, Islam.

--o--

IN 1970, THE SMALLPOX eradication campaign was in full swing, but there were still thousands of cases every year in Pakistan. For a dumb virus, the variola major virus, the cause of the more lethal form of smallpox, was proving surprisingly tenacious. Surviving for thousands of years here, this virus had become a microcosm of Buddhism, caught up in an endless cycle of reincarnation, jumping every few weeks from one human body to the next.

But the virus evolved. Every infection represented a lineage that had completed the cycle of reincarnation thousands of times—transmitted endlessly from Buddhist to Buddhist, from Buddhist to Muslim and then from Muslim to Muslim. In recent years, a new lineage had emerged, producing a slightly different profile of proteins and behaving differently when grown in the laboratory. It might even have been a little more virulent. It was to spread as far south as Vellore in India and was to track through the Middle East before jumping into Yugoslavia, deep within Europe.

In February 1970, two samples of the new lineage were taken from patients in Pakistan, one from a three-year old boy called Abid (who, if alive, would now be in his forties), the other from an eighteen-year old man called Taj (who, if alive, would now be in his sixties). Each sample was packed full of variola major poxviruses: a million virus particles or more.

Freighted by air, these representatives of what we might call the "Abid dynasty", ascended high into the stratosphere. The viral pilgrims migrated northward from Pakistan into the heart of the Soviet Union. There, they joined an elite set of reference strains, sent to research centres around the world. Within a few years, the Abid lineage had colonised laboratories in three continents, including the laboratory of Professor Keith Dumbell at St. Mary's Hospital Medical School in London, On 26th May 1978, the Abid lineage made the hundred-mile journey from London to Birmingham.

--o--

FREED FROM THE ENDLESS CYCLES of host-to-host transmission—from the samsara of entry, infection, and escape from human flesh—the Abid Dynasty had achieved viral enlightenment, nirvana in the laboratory. Whether propagated endlessly in a paradise of laboratory culture or left to sleep frozen or freeze-dried, the virus had become immortal, tamed, other-worldly.

But within twelve weeks of its arrival in Birmingham, there would be a convergence of the twain: virus and victim. The virus was to escape back into the real world, the wild world of human flesh and blood. And when it did, it would call to mind a concept not from Buddhism, but from the newer faith of Islam: YAWM AD-DIN or JUDGMENT DAY.

A Child is Born, ENGLAND, 1938

The world is on the brink of a World War. A baby girl, called Janet, is born to Hilda Whitcomb and her husband Frederick. Smallpox still looms large on the world stage, menacing every continent and almost every country. In a broad swathe of territories bounding the Tropics, from Brazil via sub-Saharan Africa and the Indian subcontinent to Indo-China, the most severe form of smallpox, variola major, is still a clear and present danger, killing 30% of those it infects. Most of those that aren’t killed are left blind or horribly scarred for life.

Curiously, in the West, for several decades, a milder form of the disease, variola minor or alastrim, with a death rate of less than 1% had taken root. But globally, there were still tens of millions of cases, millions of deaths that year from smallpox. With smallpox packed into humans of every creed and colour, the planet carried a viral load of variola virus that topped ten thousand million million virus particles. There were more smallpox virus particles on Earth than there were stars in our home galaxy, the Milky Way. But within the lifetime of that baby girl Janet every viral star in the variola firmament will be extinguished. And she will play her own tragic part in our story.

A couple of snippets from the Preface

Here are a couple of snippets from the Preface.


The M5 Motorway, England 

England’s M5 motorway is not particularly notable. It wasn’t the country’s first motorway to be built, nor is it the longest—those honours both go to its northerly neighbour, the M6. But it has a hidden importance, as it links the Gloucestershire village of Berkeley to Britain’s second city, Birmingham: the beginning-of-the-end and the end-of-the-end of smallpox. Historically, a full nine score years and two separate Berkeley from Birmingham, but by a curious twist of fate, geographically they are less than sixty-six miles apart—a short drive of just an hour and twenty-three minutes, most of it along the M5.

On 14 May 1796, at his home in Berkeley, the English scientist Edward Jenner inoculated James Phipps, the eight-year-old son of his gardener, with material from cowpox blisters on the hand of Sarah Nelmes. A short while later, he challenged him with material from a smallpox patient and found that the boy was protected against the deadly infection.

Ten years later, Thomas Jefferson, founding father of the American Republic, wrote in a prophetic letter to Jenner ‘Future generations will know by history only that the loathsome smallpox existed and by you has been extirpated.’ The last naturally occurring case of smallpox was diagnosed in Ali Maow Maalin, a hospital cook in the picturesque seaport of Merca, Somalia, on 26 October 1977.

---0---

In August 1978, the smallpox virus crept like a thief in the night from a laboratory in Birmingham to reinhabit human flesh and blood. But, fortunately, more than thirty years on from those last days of smallpox in Birmingham 1978, Jefferson’s dictum is now an established fact: most of the population knows smallpox only from the history books.

In this book, I set out to give an account of the 1978 Birmingham outbreak, drawn from records of the time and the reminiscences of some of those who lived through it. To put that last outbreak in context, I provide an series of additional vignettes from the life of this vanquished virus. Writing for the English-speaking world, I have focused primarily on what happened when this virus repeatedly struck Britain during the twentieth century.

The twenty-first century reader will find the Britain haunted by smallpox both a familiar place, with its school trips and pubs, youth clubs and folk dances, and, at the same time, an unfamiliar place, where there was no Internet, no mobile phones, no DNA sequencing, and no modern immunology or cell biology."

...


It is easy to look back at the ten years leading up to 1978— the tail end of the sixties and the seventies that followed and—as a decrepit decade, a time of dreary deadlock and a world divided. The assassination of Martin Luther King. The Vietnam War and the Cold War. The Oil Crisis. Industrial discord, frequent power cuts, the three-day week and the IRA’s mainland bombing campaign. 

But let’s not forget that this was also a time when Americans sent men to the moon “in peace for all mankind” and celebrated their bicentenary with photos from the surface of Mars. This was a time when cold war adversaries shook hands in space and the first space station orbited our planet. This was a time when humankind sent Voyager probes off on a grand tour of the solar system, turning half-glimpsed smudges in the night sky into newly mapped worlds. This was a time when we humans first began to refashion the genetic legacy of nature to our own ends and laid the foundations of the home recording and computer age. This was a time before the mind virus of neoliberalism infected our politics; when British society stood at a peak of equality unseen before or since. This was a time when we could fly from London to New York on Concorde in three hours, faster than the speed of sound, and arrive before we set off.

And let’s also not forget that this was a time when we took on a microbial adversary that had killed more humans than all the wars in history—and won! 

This was a time when we drove a vicious virus out of every ounce of human flesh on the planet.  

These were the last days of smallpox! 

The Game's Afoot!

On this date in 1796, at his home in Berkeley, the English scientist Edward Jenner (left) inoculated James Phipps, the eight-year-old son of his gardener, with material from cowpox blisters on the hand of a milkmaid Sarah Nelmes and set in motion a train of events that led to the eradication of smallpox. It is thus a fitting date for me to announce that I am writing a book entitled The Last Days of Smallpox, which not only covers events in Birmingham in 1978, but also several other twentieth-century smallpox outbreaks, with details of context and reactions. In many interesting ways, these outbreaks hold up a mirror to the society of the time, but also resonate with our own times.

Like my previous book, The Rough Guide to Evolution, this is a labour of love, which I am having to fit in around my usual academic work of doing research and teaching, writing papers and grants. I have now managed to get 30,000 words down on the page, which gives me the confidence to believe I will actually get this book written, although there is still much more to do. But I think I am now ready to let others join me in this adventure, so that on this blog I will share my journey as an author and also release drafts of some parts of the book in the hope of eliciting constructive comment, garnering a few words of encouragement to keep me going and whetting the reader's appetite for the completed work!

In this age of disintermediation, I am aiming to self-publish via Amazon or some equivalent service, but sorting all that out, together with marketing of the book will also be an adventure worth sharing.

To start the ball rolling, the next few posts will be samples from the current draft of the book. Later, I will share my experiences in finding sources, witnesses and information and, maybe, even get readers to help me in my research.