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Authors: M.D. Kevin Fong

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Based in Vietnam with the World Health Organization, Urbani had been called in to advise physicians at the French Hospital in Hanoi on February 28. There a Chinese-American businessman named Johnny Chen had been admitted, suffering with an unusual and serious flulike illness. Urbani was unsure of the identity or nature of the disease; it behaved unlike anything he had seen before. As Chen's condition deteriorated, Urbani's concern at the strangeness of his illness grew. Within days, members of the medical team who had been in contact with Chen were also falling ill and exhibiting the same constellation of symptoms. It was clear to Urbani that they were dealing with a new and potentially dangerous infectious disease.

Chen, a man in his midforties, had a high fever and what looked like severe pneumonia. But other organ systems were also involved: His blood pressure was dropping, and his kidneys were showing signs of compromise. The medical team investigated further, but none of the usual suspects was present; bacteria were absent from his bloodstream, and the course was too aggressive to be ordinary viral influenza in a reasonably young, previously healthy man. The disease was a mystery. It was without a name, a known cause, or a point of origin. Without these it would remain without a treatment, a vaccine, or a means of containment. And if, as seemed likely, it proved lethal to Chen, then Urbani would be looking at an unknown, fatal, and highly infectious disease in a man who had traveled halfway across the world aboard a sealed jet aircraft, making countless contacts on the way.

Reports of a severe and atypical pneumonia sweeping across the southern provinces of China had been circulating for some months, but details and reliable data had been frustratingly hard to come by. Chinese officials had initially played down the scale of the outbreak, stating that the number of cases ran to little over three hundred, with only five deaths among these. This implied that the mystery illness was of little concern and would most likely burn itself out. But the true extent of the outbreak had been disguised. Later the world would learn that over eight hundred people had become infected in China in those early months, and more than thirty had died. But in February 2003, Urbani and the medical team at the French Hospital in Hanoi knew nothing of this.

Urbani spent the next eleven days working closely with the French Hospital in Hanoi. He first told the staff how best to protect themselves with the equipment they had available. At this time, they had little more than gloves, hand basins, and medical masks, but Urbani impressed upon them the vital importance of these basic measures. As concern grew among the hospital staff, Urbani provided reassurance through his continued presence. He returned every day and worked late into the night. Through these efforts, he built trust and later persuaded the hospital to take the difficult step of quarantining those members of staff with symptoms away from the wider Hanoi public. Shortly afterward, the French Hospital was closed to the public and armed guards were posted outside its front doors.

Urbani's instincts told him that this was something very strange and very dangerous—something other than flu. He pursued lines of inquiry relentlessly, working long days at the French Hospital, taking samples, running tests, and making sure that infection-control protocols were properly enforced. Containment and proper identification of the causative organism were his priorities. The war against this infectious disease, whatever it was, would turn on these simple measures.

Pascale Brudon, the head of the World Health Organization's regional office in Hanoi, witnessed Urbani's efforts and was in touch with him throughout. She was concerned for his safety and anxious that he should take proper steps to protect himself. Urbani understood the risks he ran but regarded it as his duty to help the clinicians at the French Hospital amid this terrifying outbreak. Between them Urbani and Brudon saw to it that the WHO's headquarters in Geneva was alerted. If their instincts were correct, then the fallout from this disease would be felt all over the world.

Over the next few days, international experts, summoned by the Vietnamese government on Urbani's recommendation, arrived in droves. By this point, Brudon could see that Urbani was exhausted. He had for that past fortnight been alone in the fight to identify and contain this disease and now clearly needed to rest. Brudon suggested that Urbani could now afford to take a break and attend a conference in Bangkok, where he was due to give a lecture. Fatigued, Urbani accepted, and on March 11, 2003, after handing over to the incoming teams from the WHO and the United States' Centers for Disease Control (CDC), he boarded a plane at Hanoi airport.

Aboard the flight, Urbani developed a fever, a dry cough, and a headache. In those hours, confined aboard that aircraft, he could have been under no illusions about his ailment's likely cause. After the plane touched down, Urbani found his way through to the arrivals hall, where a colleague from the CDC was waiting to greet him. Fearing the worst, Urbani urged him not to approach. While they waited for an ambulance to arrive, the two men sat apart in silence. The paramedic team arrived wearing masks and protective clothing and took Carlo to the hospital. He died eighteen days later.

—

I
N THE SAME WEEK
that Carlo Urbani left Hanoi, Johnny Chen, the forty-eight-year-old businessman whom Urbani had first been called to see, died in intensive care after having been transferred to Hong Kong.

Days later, Jean-Paul Derosier, a sixty-five-year-old French anesthetist who had treated Chen, along with a nurse who had been involved in his care, also died of the same disease. By March 15, authorities were aware of forty-three cases in Hanoi. Of these, forty-two were health-care workers who had looked after Johnny Chen. The exception was the son of one of the infected hospital staff. Among these, five had deteriorated rapidly, eventually needing intensive care and artificial ventilation.

The WHO had also become aware of new cases worldwide, in Singapore, Taiwan, Canada, and Hong Kong. In the week that Carlo Urbani was admitted to an intensive-care unit in Bangkok, the WHO issued a global health warning for the first time in its fifty-year history. The disease, whose precise nature was still a mystery, would finally get a name: severe acute respiratory syndrome, or SARS.

By the time of the WHO's health warning, this much was known: The disease was infectious, highly transmissible, and deadly. Health workers on the front line and their families were most at risk.

Due in large part to the efforts of Urbani in the early days of the outbreak, the origins of SARS were rapidly established. It emerged that Johnny Chen had traveled from Hong Kong; there he had stayed on the
ninth floor of the Metropole Hotel. Here he and seventeen other guests had acquired SARS from a single individual. Dr. Liu Jianlun, a sixty-four-year-old Chinese medical professor, had unknowingly contracted SARS in Guangdong while treating patients. He had traveled to Hong Kong to attend his niece's wedding. This journey from the southeastern provinces of China to Hong Kong was the triggering event in the global outbreak that followed. Room 911, the room occupied by Dr. Liu, became the centerpiece of the investigation, and the
ninth floor of the Metropole became ground zero for SARS.

The virus had circulated in animals for many months. Virologists chased its origins back to civet cats. In the food markets of Guangdong, with their exotic animal husbandry, it had moved from animal species to animal species before finally making the jump into humans.

Precisely how it did this remains a fundamental question for the science community. The limited repertoire of genes that the virus possesses is able to mutate and reassort. It is like the badly copied blueprint for a curious device, handed down from one generation to the next. Offspring are able to share new innovations or spontaneously improvise, until finally enough of those alterations align and sum to produce a terrible weapon. Nature, as our virologists are fond of reminding us, is the best and most efficient bioterrorist.

But SARS would have likely remained endemic within the southern provinces of China, had it not been for the fateful journey of Dr. Liu Jianlun. Taking it to Hong Kong, to an international business hotel, provided the most efficient vehicle for the spread of disease. At that nodal point, Jianlun was confined and in contact with dozens of travelers, all of them passing through, many on their way to other international destinations. From the moment Jianlun checked in to the Metropole Hotel, SARS was set to go global.

—

SARS
, AS ITS NAME SUGGESTS,
first affects the respiratory system. But unlike polio it does not target the mechanics of breathing but the substance of the lung itself. The virus binds to cells in the tissues of its fragile air sacs and the branching network of airways. The virus enters and forces these cells to start churning out millions of new copies, like a printing press turned over to the production of quick and dirty war propaganda. The cells are not entirely without response. They are able to signal that they are compromised and summon the immune system to attack. But the virus is buried deep within the structure of the cell, and so destroying it means destroying the cell in its entirety: collateral damage in the wider fight against disease.

A combination of the death of these infected cells and the scarring and inflammation that accompanies the immune system's attack leaves the substance of the lungs compromised. The once tissue-thin membranes, capable of expanding and collapsing like a supple balloon, become more rigid and less compliant. The exchange of oxygen and carbon dioxide across their surfaces is obstructed, and the force needed to expand the chest and perform the work of breathing is massively increased.

To the physician called to see a patient deteriorating in the face of SARS, the signs are all too clear. Effortless healthy breathing is replaced by a rapid, shallow pattern. Other muscles not usually involved in expanding the chest are recruited to overcome the stiffness brought by the viral infection. All of this additional mechanical effort needs to be paid for. The body's demand for oxygen increases at the same time as its ability to grab those molecules of oxygen from the outside air and exchange them through the thickened, diseased membranes of the lung worsens.

Hemoglobin, the molecule in the blood cells that carries oxygen, is bright red in appearance when fully laden. Once stripped of this oxygen load, it becomes duller and bluer—accounting for the difference in appearance between arterial and venous blood. But if arterial blood cannot acquire a new, full load of oxygen in the lungs, it loses its rosy hue. The skin through whose capillaries these blood cells course acquires a shade more akin to thundercloud gray.

It is that vision—of the gray, breathless patient with the thousand-yard stare—whose first glimpse, even in the half-light of a hospital ward at night, signals real trouble and the need for interventions that can be provided only by intensive care. When the supply of oxygen is outstripped by demand, critical illness and death will inexorably follow. In these circumstances, the bridge to survival is provided by modern intensive care.

—

C
HARLES
G
OMERSALL WAS
at the end of another shift as consultant in charge of the intensive-care unit at the Prince of Wales Hospital in Hong Kong. He had worn his hard-shell mask all day; its metal pinch clip had dug itself into his face, leaving a reddened dent in the bridge of his nose. But even now, striding across the car park, away from the ward and main hospital building, he kept it in place. The past fortnight had been punishing. The SARS outbreak was now at its height, and the unit was under strain from the constant flow of cases in need of critical care.

His first week on duty during the epidemic had been sobering. As an experienced intensivist, he was familiar with destructive pneumonias and deranged physiologies and used to holding the line in the face of adversity, but SARS had a different character. The clinical course was so fierce that at first Gomersall wondered if any of his infected patients would manage to survive.

The damage to the respiratory system wrought by the virus was severe. Artificial ventilation had to be applied with care. Forcing stiffened lungs open with external pressure from a ventilator was not without its hazards. Titrating the volumes and pressures applied by the mechanical ventilators precisely against the needs of each individual patient was an art. Getting it wrong could rupture delicate membranes, causing pneumothorax and a life-threatening collapse of the lungs. Ventilating too hard, with overzealous volumes, could further inflame the lungs and the situation. But it was the impact of SARS upon the rest of the body that presented the biggest challenge.

—

T
HE CELLS OF THE IMMUNE SYSTEM
roam the bloodstream and tissues, like policemen pacing the beat. They detect potentially harmful microbes, attack them, and then beckon other immune cells to enter the fray. When activated appropriately, this system puts a stop to trouble before it has a chance to get out of hand. But this system can be all too responsive. Some infections—SARS among them—overstimulate the immune response, giving rise to widespread inflammation that in turn can harm the body, an inappropriate response that causes more damage than the original infection itself ever could have.

Because of this, Gomersall's SARS patients endured more than simple respiratory failure. The storm of immune response damaged kidneys and livers and caused hearts to fail, which meant multiorgan failure also had to be supported.

In the years since Ibsen's first intensive-care unit was established, medical technology has moved on to allow the carefully nuanced support of many organs besides the lungs.

Now the failing circulation can be supported with noradrenaline, which raises sagging blood pressure. The heart can be driven with infusions of adrenaline, boosting its contractile force and ejecting greater volumes of blood needed to perfuse the rest of the body. Medicine has learned how to replace the work of the kidneys, using dialysis machines and blood filters. Even a malfunctioning gut can be augmented with a feeding tube or replaced by running calories and nutrients directly into veins. Today all of this can be achieved artificially and, in the most dangerous days of the disease, with patients in a state of anesthesia and unaware of their plight.

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