Outwitting a Virus

"The disease we know as the flu is caused by the influenza virus, which mostly lives in fowl and pigs; humans catch it through close contact with those animals."
"The 1918 outbreak was caused by an H1N1 variant that was first noticed in an army camp in the United States."
"It's hard today to describe the speed of the virus's spread and the scale of its staggering devastation."
Mike Callaghan, medical anthropologist, Switzerland

The 1918 flu pandemic is sometimes called “The Spanish Flu” not because it originated in Spain, but because that nation had remained neutral during the war and freely reported news of flu activity.

"The 1918 flu pandemic occurred during World War I; close quarters and massive troop movements helped fuel the spread of disease."
"In the United States, unusual flu activity was first detected in military camps and some cities during the spring of 1918. For the U.S. and other countries involved in the war, communications about the severity and spread of disease was kept quiet as officials were concerned about keeping up public morale, and not giving away information about illness among soldiers during wartime. These spring outbreaks are now considered a “first wave” of the pandemic; illness was limited and much milder than would be observed during the two waves that followed."
"In September 1918, the second wave of pandemic flu emerged at Camp Devens, a U.S. Army training camp just outside of Boston, and at a naval facility in Boston. This wave was brutal and peaked in the U.S. from September through November. More than 100,000 Americans died during October alone. The third and final wave began in early 1919 and ran through spring, causing yet more illness and death. While serious, this wave was not as lethal as the second wave. The flu pandemic in the U.S. finally subsided in the summer of 1919, leaving decimated families and communities to pick up the pieces. Scientists now know this pandemic was caused by an H1N1 virus, which continued to circulate as a seasonal virus worldwide for the next 38 years."
 

What was familiarly called the "Spanish flu" was a pandemic; it broke out all over the world. A world at war. Where, it was explained, an aggregation of people in close quarters helped its swift spread. Great swaths of military personnel were moved around from country to country, helping the virus which turned deadly, to spread with swift ease. At one time, it would be mostly country people, people who lived and worked on farms and had close contact with animals and birds who were at risk and the spread of the virus was limited because they remained where they were, locally.

At the very time that the world is remembering the two great world wars that brought death and destruction to the global community, the hundred-year anniversary of the start of the First World War, considered in its wholesale death toll, to be 'the war to end all wars' is being recognized. In lock-step with that global conflict was the global affliction of the "Spanish flu". Spain, as a neutral country at the time of World War I, had no restrictions imposed on news of the influenza epidemic it was suffering, unlike those countries at conflict who kept the news from their public already struggling with the demoralizing stories out of war zones.

That strain of influenza destroyed more lives than both world wars' totals of military and civilian deaths as consequences of the two global conflicts. In the first six months of the flu's onslaught close to 50 million people died worldwide. By the time it was over, when no further waves of infection occurred, an estimated 100 million people were dead as a result of the flu. It was not the flu we face yearly with its recognized symptoms that puts people low for several days to weeks. This was a pathological scourge that killed.

When one in three people world-wide became infected and died, combating armies became short of fighting men. Half their soldiers were bedridden. Civilians were instructed to wear face masks at all times. Eventually the lethal strain wore itself out by 1920. Since then medical science has been anticipating another massive viral flu outbreak with dread. But the combination of contagious impact and lethality has not yet been replicated. And the yearly recommendations that populations be inoculated against the flu has its genesis in hopes of averting a worst possible scenario.

People with compromised immune systems, people with chronic illness and disease, the elderly and the very young depend on the herd immunity concept; the greater the numbers of people for whom the onset of illness through the impact of protective inoculation the less likely the possibility of a widespread breakout in a largely unprotected population. In 1918's globalized flu pandemic populations with no immunity were suddenly exposed to the virus. Because of the war populations migrated, both military and civilian.

At that time long-distance travel was accomplished through rail and ship primarily. In our modern era with rapid transit where airline passenger jets can traverse the globe in hours, not weeks, where products are shipped globally and with them germs are transmitted with incredible speed. That speed accomplishes an amazing feat of transmission by a virus that reacts swiftly to impediments. Each year a combination of the commonest flu strains prevalent in China the year before is produced in the hope that the following year's strain would be closely aligned for successful immunity.

The flu virus is a swiftly mutating trickster, shifting in response to the presence of any remedy produced to impact its deadly efficacy. By the time a vaccine is produced the virus has undergone change and becomes more effective in its deadly delivery. Because it is so capable of mutating to meet the challenges meant to destroy its efficacy, it is always one step ahead of remedies to modify its effectiveness and potentially bring its impact to a halt, boosting the body's immune system to deflect its ingress.

It has proven itself adept at developing new strategies to resist medication, to survive in new environments and to negate its transmission. It is a formidable foe for medical science, a medical community anticipating that a day will arrive when it will once again forcefully impact on a global scale with deadly precision. There is no global conflict ongoing at the present time, other than an increasingly chilly 'cold war', to enhance and invite a viral outbreak in response to a dense gathering of warring factions worldwide.

But there are other types of wars, in a world where trade and economics and mercantile interests come into play. Such as sanctions as punishment by one entity against another in a conflict of a different kind. The current trade war between the United States and China has been a complicating factor in stalling the ongoing trade between China's production capabilities and its far reach throughout the world where its products are always in demand. Among other items that are in demand is China's cooperation in providing intelligence on flu strains.

China's ownership of this intellectual property has enabled it to turn its sole-source data into a critical bargaining chip, one that leaves vaccine researchers struggling to come up with a combination that will present as a deterrent to this year's flu strain -- without the vital data it depends upon from China.
Researchers in pathogen transmission know that should a deadly new strain of flu arrive it would impact their capacity to mobilize resources quickly and effectively to combat airborne, contagious, fast-acting viruses.

To succeed, however, there must be a scaffolding comprised of cooperation, restraint and above all unprecedented levels of research focusing on a virus whose reactive abilities and mobility are frighteningly legendary.

Ready and willing, these volunteers were on the forefront of the 1918 pandemic response. Today, influenza viruses continue to pose one of the world’s greatest health challenges.

A Deadlier Ebola

"It's very difficult to prove that a mutation like this is responsible for the severity of the epidemic ... But it would have to be a pretty amazing coincidence."
"We think that the mutation is actually an adaptation to humans [excluding adaptation to infect the assumed reservoir animal harbouring Ebola, bats]. It's kind of a signal to us that this mutation was selected for replication of the virus in people, which I would argue is further evidence that this mutation is significant and is not just a coincidence."
Jeremy Luban, virologist, University of Massachusetts Medical School

"As virologists we weren't really convinced [that the virus hadn't adapted. We thought ... some of these changes might be affecting the biology of how the virus behaves."
"Once it's in humans, that's the new host. It's really got to acquire adaptations and get the most fit for in human-to-human transmission."
"We feel that the two papers together make a really powerful case."
"We know that these viruses are causing human infection, we know that they're evolving, but do we really know what that evolution means?"
Jonathan Ball, professor, University of Nottingham, England

A burial team at work during the West African Ebola crisis in Liberia in 2014. Researchers now believe that a genetic mutation may have made one strain of the virus more suited to entering human cells.  (DANIEL BEREHULAK / The New York Times)

Drs. Jeremy Luban and Jonathan Ball each led a team of investigators and independently of one another produced a study that turned out to reach like conclusions. As it turned out the two teams of virologists had their studies published in the journal Cell. Their studies identified a mutation that altered Ebola haemorrhagic fever virus; at least that part of it that infiltrates receptors on the outside of the host cell; that host cell that is in humans, to make it more infectious and more lethal.

The West African outbreak that concerned scientists and medical professionals and governments between 2013 and 2016 menaced vulnerable people in rural and urban areas of West African, killing over 11,300 people before it was wrestled to a standstill through the international community of medical professionals and research scientists focusing on the outbreak declared by the World Health Organization to have become a pandemic, a public health emergency. Although it struck hardest in Africa it also appeared in Britain and Sardinia, and secondary infections occurred worryingly in the United States and Spain.

The research conducted by Dr. Luban led him to the conclusion that the mutant versions were "better at fitting into the lock [receptors on the host cell] and got into the cell better". Having infiltrated the cell the virus succeeded in reproducing itself to get on with its deadly work, the purpose of its existence. It took mere months for this mutated strain to dominate the epidemic where some 90 percent of those who became affected did so through the mutant version of the virus.

Beginning in Guinea in late 2013, it remained unknown why a hundred times greater numbers of people became infected in comparison to any other previous outbreak of the virus. It was estimated that in the course of 28,000 infections the virus mutated enabling it to infect more people, a function of reproduction. Natural selection served to aid the mutation to spread its deadly effects. What threw scientific study off was the hardest hit areas also had the worst public health infrastructure.



The researchers reconstructed the evolution of the Ebola virus, identifying where the pathogen began its genetic alterations. One mutation, a single nucleotide change on a gene whose purpose was to build the glycoprotein "key", appeared to have been persistent, and it was this altered gene that their attention focused on. The research team led by Dr. Ball attached the mutant glycoprotein to another virus entirely to test its capacity to infiltrate host cells.

The finding was that the mutant was infinitely more efficient entering human cells and those of other primates in comparison to the standard version. But the vector that harbours Ebola in between human outbreaks appeared not to have been infected by the mutant; its specialty remained the invasion of human cells. Coincidentally, Dr. Luban whose normal field of study is HIV infection, was in the process of an unrelated experiment on a number of viruses which happened to include Ebola when he noted one variant of Ebola appeared proficient at infecting cells.

Dr. Ball, liaising with epidemiologists, identified the variant as a mutant that appeared early in the outbreak, and then spread throughout the affected region. The realization struck both researchers only after their teams wrote up their findings for publication, that they had identified the same mutation, which they named glycoprotein mutant A82V. The mutant, it is felt, likely wiped itself out finalizing the outbreak.

Meant specifically to infect human cells, it was not recognized as a threat able to retreat into the reservoir population of bats to be resurrected at some later time.