A cure for flu (from beyond the grave)

Eighty-nine years after he died in a flu pandemic, the body of Sir Mark Sykes was dug up last week – in the hope that his uniquely preserved remains may help provide a weapon against the killer virus. By Cahal Milmo

(PA)

At a solemn service before sunset in a rural Yorkshire churchyard eight days ago, a battered lead-lined coffin was reburied hours after being opened for the first time in 89 years. As prayers were recited, samples of the remains of Sir Mark Sykes, the aristocratic diplomat and adventurer whose grave had been exhumed, were being frozen in liquid nitrogen and transported to a laboratory with the aim of saving millions of lives.

During his life, Sir Tatton Benvenuto Mark Sykes succeeded – quite literally – in leaving his mark on the world map. As the British government's lead negotiator in a secret 1916 deal with France to carve up the Ottoman Empire, he laid the groundwork for the boundaries of much of the present-day Middle East and, according to some critics, its current conflicts.

But it was the manner of the death of this Conservative MP, British Army general, and father of six children, that may yet prove the source of his most significant legacy by providing key answers in how medical science can cope with the 21st century's first lethal flu pandemic.

While negotiating terms of the peace negotiations to end the First World War in Paris early in 1919, Sir Mark became one of the estimated 50 million victims of the so-called Spanish flu and died in his hotel near the Tuilleries Gardens. Like many victims, he was in his prime at just 39.

His remains were sealed in a lead-lined coffin, according to the customary practice of the era, and transported to Sledmere House, the handsome stone mansion in east Yorkshire which has served as the Sykes family seat since the 1780s. He was buried in the graveyard of St Mary's Church, adjoining the house.

Were it not for the fact that Sir Mark's body was hermetically sealed by a thick layer of lead, the story of his life would have passed quietly into history.

But the accident of chemistry – the decay of soft tissue encased in lead is dramatically slowed – has presented scientists investigating ways to deal with the inevitable mutation of the H5N1 "bird flu" into a lethal human virus with a unique opportunity to study the behaviour of its predecessor.

The 1918-19 epidemic was caused by an avian virus, H1N1, which is similar to H5N1. Scientists believe it could hold valuable information about how the flu bug makes the leap from animals to humans.

But there are only five useful samples of the H1N1 virus around the world and none from a well-preserved body in a lead-lined coffin. H1N1 has already been sequenced by scientists using frozen remains found in Alaska but many questions remain about just how the virus killed its victims, and the way it had mutated by the time it killed Sir Mark.

Professor John Oxford, the leading virologist based at Queen Mary's College in London, who led the team investigating Sir Mark's remains, said: "He died very late in the epidemic, when the virus had almost burnt itself out. We want to get a grip on how the virus worked both when it was at its most virulent and when it was coming to the end of its life.

"At a time when we are on the verge of the first influenza epidemic of the 21st century, the samples we have taken from Sir Mark have the potential to help us answer some very important questions."

The two-year process of gaining permission from the Diocese of York to carry out the exhumation, involving a special hearing presided over by a High Court judge, and then planning a disinternment with full bio-hazard security precautions, came to its end on 8 September when medical experts, clergy, environmental health officers and the family of Sir Mark gathered to begin uncovering his grave.

Due to a requirement of the diocese that the exhumation be carried out in strict privacy, confirmation that it had taken place was given only yesterday.

After a short prayer, the gravestone was removed and the coffin uncovered inside a sealed tent before researchers wearing protective suits and breathing apparatus opened the casket. The Independent understands that a crack was found in the top of the lead lining, meaning that the chances of finding a pristine sample of the virus are now remote. A study of the tissue samples taken from the remains will, however, reveal valuable genetic imprints of H1N1 and its condition when Sir Mark died.

Among the riddles that scientists still have to answer is the precise mechanism of how Spanish flu, which actually originated from a bird in France, killed the people it infected, whether by a lethal viral infection, a combined viral and bacterial infection, or a cytokine storm – where the virus sparks an overwhelming immune response and causes the body to attack itself.

It will take several months to study the 17 samples taken from Sir Mark's remains before any new findings are confirmed from the exhumation project, which has been chronicled by BBC1's Inside Out documentary series.

Professor Oxford, who is investigating the possibility of exhuming another set of remains from the 1918-19 epidemic, said: "Scientists worldwide are working on examples of the virus from the remains of five people... so any additional source is very significant. What we are after from Sir Mark is a genetic footprint from the virus at the time he died. It has the potential for us to be able to say with regard to H5N1, 'It's ok, we can relax', or 'Oh my God'."

Sir Mark's descendants are delighted that his influence may reach a different sphere of human endeavour. His grandson, Christopher Sykes, said: "We were all agreed that it was a very good thing and should go ahead. It is rather fascinating that maybe even in his state as a corpse, he might be helping the world in some way."

The threat to millions of lives

Once in a generation the virus that causes ordinary flu undergoes a major mutation to create a wholly new strain to which no one has immunity. That triggers a pandemic that can – and has – caused death and illness on a Biblical scale.

Three times in the 20th century flu pandemics have claimed millions of lives worldwide. The last one was in 1968. Experts say the next one is overdue. "This will come, it will be real and only if we plan can we reduce its impact," Sir Liam Donaldson, the Government's Chief Medical Officer, has said.

In 1968 and in 1957 the pandemics were relatively mild, killing fewer than 50,000 in Britain; the average winter flu death toll is 13,000 to 26,000.

However, the 1918 pandemic emerged as the First World War was ending, reaching Glasgow by May 1918 and London in June: 228,000 people died in Britain; worldwide it claimed up to 40 million lives. The next could be worse. The H5N1 avian flu virus, which emerged in 1997, can infect humans and has a death rate of more than 50 per cent. A small tweak to its genetic make-up could create a strain that would sweep the world. A pandemic strain is expected to lose much of its lethality as it gains in infectivity. But even a 2.5 per cent fatality rate, as in 1918, would translate to millions of deaths. Sir Liam says that up to 750,000 lives might be lost in Britain.