Early this summer, vials of inactivated Ebola virus from Sierra Leone began arriving at Harvard, packed in dry ice. Scientists on the Cambridge campus worked in round-the-clock shifts to analyze the contents of the vials.
Their work was urgent -- and deadly serious. The researchers oscillated between a rush to unravel the genetic fingerprint of the lethal virus and the vain wish that time would slow down, as they learned that the same scientists in Africa who had collaborated with them were now being felled by the disease.
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'We wake up, we learn some news, we bawl our eyes out and we try and figure out what we can do,' said Pardis Sabeti, a computational biologist at Harvard University who supervised the work.
On Thursday in the journal Science, the team of scientists -- including five African colleagues who have died from Ebola -- published the richest and most detailed portrait of the virus yet that is ravaging West Africa.
The report on Ebola samples taken from 78 infected patients in Sierra Leone reveals a myriad of small ways the pathogen has changed, accumulating 341 new mutations that set it apart from past outbreaks.
The study also shows that the virus spread into Sierra Leone in late May, when a dozen women attended the funeral of a healer who had been working in Guinea. Those women brought back from the funeral, the data reveals, two slightly different strains of the virus.
As the scientists have made their discoveries, those findings have been made available nearly in real-time. Ebola samples would arrive in Cambridge and within two weeks, highly specialized equipment at the Broad Institute would generate genomic blueprints -- a remarkable timeline, outside researchers said.
A decade ago, 'if we had outbreaks, whatever the outbreak was -- dengue or chikungunya -- two years after the epidemic, you would say scientists working for the past two years have now shown this original strain now originated in Indonesia, whereas now in real time as the epidemic is going on, we're able to do that pinpointing in the most elegant specific and sensitive manner,' said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. 'From a scientific standpoint, that is phenomenal.'
'There are two sides of it,' said Sabeti, who lead the research with a scientist from Tulane University and the late Dr. Sheik Humarr Khan of Sierra Leone, a specialist in treating viral hemorrhagic fevers who was infected with the virus and died in July. 'My lab has never been this sad and never been this motivated since I started it.'
But because of the speed with which the findings are being generated and made public, scientists have had little time to draw many conclusions. Keeping the genomes private so that Sabeti and her lab could examine them fully first -- as is traditionally done in science -- wasn't an option. They began posting the genome sequences of the virus online in late June, in the hope that crowdsourcing the problems to laboratories around the world could more rapidly lead to insights that might help halt the spread of the outbreak.
Outside scientists said the genomes will provide clues that could help check whether diagnostic tests used to detect the disease are keeping up with the mutating virus. They also allows scientists to trace the lineage of the virus, which they now believe diverged from a Middle African strain of Ebola in 2004.
The data also show how rapidly the virus is mutating; past outbreaks have burned out quickly and so have not given the virus as much of a window to change in ways that might make it more of a public health threat, making it important to keep an eye on how it is changing, Fauci said. So far, researchers have not seen evidence that the mutations are making the virus more dangerous.
The researchers have already discovered that five standard tests used to diagnose Ebola in blood samples are not a perfect match for the current strain of the virus. Now, they are testing whether those differences would have an effect on the test being able to certify that someone has the virus.
'A small degree of variation can have a significant public health impact, depending on where it is and what it causes in the virus,' said Dr. Daniel Bausch, an associate professor in the department of tropical medicine at Tulane School of Public Health, who was not involved in the work.
Bausch compared the diagnostic tests and the virus to a key and a lock that need to match up in order to work. If there's a nick in the part of the key that goes in the lock, the door may not open; but if the nick is in the handle of the key, it will still work. Right now, it's not clear whether the genetic changes the researchers have detected are in the handle or the body of the key -- and, thus, whether they would affect the tests.
Thomas Geisbert, a professor of microbiology and immunology at the University of Texas Medical Branch in Galveston, said that he didn't immediately see any mutations that would affect the ability of ZMapp, an experimental therapy that has been used in several patients, to work.
The collaboration was made possible by a close relationship between Sabeti's laboratory that developed for entirely different reasons. Years ago, Sabeti combed the human genome looking for genes that had been shaped by evolution. To her surprise, she found that a gene involved in infection by a hemorrhagic fever called Lassa had the strongest signal of evolution's handiwork.
She began forging partnerships and setting up the laboratory infrastructure and training to study the virus on the ground in Sierra Leone, with an interest in how the virus and people had co-evolved. Over the years and many trips to the Kenema Hospital, that academic interest has developed into a rich collaboration and a network of friendships.
When Sabeti and colleagues got word that Ebola had been detected in Sierra Leone, two scientists from her laboratory traveled to the hospital to bring with them primers, short strands of genetic material that would allow for early detection of the disease.
Stephen Gire, a research scientist in Sabeti's laboratory, returned with a team in July to streamline the procedures in the lab as the caseload has escalated.
'The burden of cases was overwhelming,' Gire said, especially in the laboratory where the workload had increased tenfold. He helped streamline procedures to ensure that workers would have time to drink water and take breaks, because working 18- to 20-hour days in protective coveralls was taking a toll on researchers.
Members of Sabeti's laboratory have not been able to travel back to Sierra Leone since July, but have been doing what they can to support friends and collaborators from afar.
'We can honor those who have died by making sure that we do everything we can to contribute to stopping this outbreak and understanding more about it for the future,' Gire wrote in an e-mail. 'And so that is why we have pushed and pushed to get this data out as quickly as possible.'
Posted by Unknown on Thursday, August 28, 2014 - Rating: 4.5
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