For months, no sequences from the virus have been released
as the Ebola epidemic sweeps through
West Africa, scientists lack key ge- netic data to answer a question that has provoked much worried specu- lation: Is the virus becoming more transmissible or more deadly, or ac-
quiring changes that would let it evade diag- nostic tests or vaccines? Thousands of blood samples from Ebola patients have been sit- ting in refrigerators in Africa and Europe, untouched. And, as Science went to press, the few groups that have new sequence data have not made them public.
Researchers are eager for a close-up look at how the virus may be evolving. Besides answering questions about its virulence, genomic data could reveal details about the epidemic, including hotspots of trans- mission and how often the virus has escaped from its animal reservoir to humans, says Andrew Rambaut, an evolutionary biologist who studies infectious diseases at the Uni- versity of Edinburgh in the United Kingdom. “If it can be done on a timely basis, you can really get insight into what is going on.” But faced with the all-consuming public health response to the epidemic, bureaucratic obstacles, and chaotic record keeping, scien- tists have had to wait.
West Africa, scientists lack key ge- netic data to answer a question that has provoked much worried specu- lation: Is the virus becoming more transmissible or more deadly, or ac-
quiring changes that would let it evade diag- nostic tests or vaccines? Thousands of blood samples from Ebola patients have been sit- ting in refrigerators in Africa and Europe, untouched. And, as Science went to press, the few groups that have new sequence data have not made them public.
Researchers are eager for a close-up look at how the virus may be evolving. Besides answering questions about its virulence, genomic data could reveal details about the epidemic, including hotspots of trans- mission and how often the virus has escaped from its animal reservoir to humans, says Andrew Rambaut, an evolutionary biologist who studies infectious diseases at the Uni- versity of Edinburgh in the United Kingdom. “If it can be done on a timely basis, you can really get insight into what is going on.” But faced with the all-consuming public health response to the epidemic, bureaucratic obstacles, and chaotic record keeping, scien- tists have had to wait.
In August, the world got its closest mo-
lecular look at the virus so far, when re-
searchers published 99 genomes of viruses
from 78 patients who were infected in or
around Kenema, Sierra Leone, from late
May to mid-June. That analysis, published
online on 28 August in Science, included more
than half of the known
cases in Sierra Leone
at the time.
The sequence data, which the researchers deposited in public databases as soon as they were generated, showed how the virus changed as it passed from person to person at the start of the Si- erra Leone outbreak, with one variant dis- appearing as another gained rominence among later cases. Since then, the outbreak has exploded into an epidemic—it has now sickened more than 13,000 and killed 5000—but the team, led by Pardis Sabeti and Stephen Gire at the Broad Institute in Cam- bridge, Massachusetts, has been unable to import any new samples from Sierra Leone.
The sequence data, which the researchers deposited in public databases as soon as they were generated, showed how the virus changed as it passed from person to person at the start of the Si- erra Leone outbreak, with one variant dis- appearing as another gained rominence among later cases. Since then, the outbreak has exploded into an epidemic—it has now sickened more than 13,000 and killed 5000—but the team, led by Pardis Sabeti and Stephen Gire at the Broad Institute in Cam- bridge, Massachusetts, has been unable to import any new samples from Sierra Leone.
Other groups have been similarly stymied.
Several researchers say that getting export
approval from beleaguered health ministries
has been tough. “I can only assume that the
system is so overwhelmed that processing
samples beyond simple diagnostic tests is
not high priority,” says Rambaut, who was a co-author on the August sequence paper.
Stephan Günther, a virologist at the Ber-
nhard Nocht Institute for Tropical Medicine
(BNI) in Hamburg, Germany, and coordi-
nator of the European Mobile Laboratory
(EMLab) consortium, says they have been
unable to export samples from Nigeria or
Liberia. But BNI has been receiving samples
from the EMLab mis-
sion in Guinea since
March and now has
close to 3000, he says.
(BNI is storing them in
its high-security lab on
behalf of the Guinean
government, which
Sabeti and her colleagues should soon
get their Sierra Leone samples, which
finally were cleared for export and
arrived in the United States last
week, says Robert Garry of Tu-
lane University in New Orleans,
Louisiana, who collaborates with
Sabeti. But to speed the research,
she and her colleagues are try-
ing to secure funding to send se-
quencing machines to West Africa.
“If we can’t get the samples here, we will get
the sequencers there,” she says. The effort
will build on the researchers’ ongoing work
with the African Centre of Excellence for
Genomics of Infectious Diseases, a consortium of universities and research institutes
in the United States, Nigeria, Sierra Leone,
and Senegal, which for several years has
been training African researchers in the use
of genomics tools.
Earlier sequence data did suggest that
the virus was undergoing rapid changes,
but that is not necessarily a sign that it is
becoming more dangerous, Rambaut says.
“Most RNA viruses mutate quickly, but ad-
aptation and functional change is a much
slower process.” Measles mutates nearly
as quickly as Ebola virus, but it has never
evolved to escape the lifelong immunity of
previously infected or vaccinated individu-
als. Even in an outbreak this big, Rambaut
says, “I see no reason to suspect the virus
will radically change its life cycle or its
mode of transmission.” ■
still owns them.)
Günther and his col-
leagues have not yet sequenced any of the samples, because consortium staff members have been busy supporting diagnostic cen- ters in affected countries. “We are all busy with fieldwork,” Günther says. “Personnel is a bit of a problem.” That should ease, he says, with a new €1.7 million ($2.1 million) award from the European Union to EMLab for Ebola research.
In France, the Institut Pasteur, where early samples from Guinea were first iden- tified as Ebola, also experienced delays exporting samples from West Africa but plans to start sequencing new viral ge- nomes soon. The institute’s lab in Dakar recently received samples from Guinea, says Felix Rey, who is coordinating the institute’s Ebola task force in Paris. The Dakar lab will extract RNA and send it to Paris for high-throughput sequencing. “We hope to have sequenced viruses from
a couple of hundred samples in the next month or so,” Rey says.
leagues have not yet sequenced any of the samples, because consortium staff members have been busy supporting diagnostic cen- ters in affected countries. “We are all busy with fieldwork,” Günther says. “Personnel is a bit of a problem.” That should ease, he says, with a new €1.7 million ($2.1 million) award from the European Union to EMLab for Ebola research.
In France, the Institut Pasteur, where early samples from Guinea were first iden- tified as Ebola, also experienced delays exporting samples from West Africa but plans to start sequencing new viral ge- nomes soon. The institute’s lab in Dakar recently received samples from Guinea, says Felix Rey, who is coordinating the institute’s Ebola task force in Paris. The Dakar lab will extract RNA and send it to Paris for high-throughput sequencing. “We hope to have sequenced viruses from
a couple of hundred samples in the next month or so,” Rey says.
Blood samples alone aren’t enough for
genomic studies. Investigators need to know
at least where each patient was from; ideally
they will also have clinical information such
as whether he or she survived. “Only when
you have those pieces of information can
you come up with useful information from
the sequences,” Günther says—and because
of spotty record keeping, that information
is often missing. He and his colleagues are
working with Doctors Without Borders and
the World Health Organization to match
samples with relevant information, but set-
ting up a database is time- and labor-inten-
sive, he says.
Meanwhile, the few Ebola virus sequences that have been generated since that ini- tial batch from Sierra Leone have not been made public. The U.S. Centers for Disease Control and Prevention (CDC) announced in August that it had sequenced Ebola virus samples from patients treated in the United States. But the data have not been placed in any public sequence repositories. That’s un- fortunate, Rambaut says. “As the U.S. cases are from Liberia and we have zero sequences from there so far, even one genome would be interesting and potentially useful,” he says. Duncan MacCannell, a bioinformat- ics specialist at CDC in Atlanta, told Science that the sequences had been “actively shared and discussed with the public health com- munity.” He says CDC is working to submit the sequences to a public database.
New sequences probably won’t show that the virus is finding new ways to attack or spread, Rambaut says. Instead, the prize is a clearer picture of the outbreak. A cluster of closely related viruses might point to a hotspot of transmission, he says, while un- expectedly diverse sequences would suggest that many cases were going undetected. Sequence data could also help researchers tell whether there has been more than one animal-to-human introduction.
Meanwhile, the few Ebola virus sequences that have been generated since that ini- tial batch from Sierra Leone have not been made public. The U.S. Centers for Disease Control and Prevention (CDC) announced in August that it had sequenced Ebola virus samples from patients treated in the United States. But the data have not been placed in any public sequence repositories. That’s un- fortunate, Rambaut says. “As the U.S. cases are from Liberia and we have zero sequences from there so far, even one genome would be interesting and potentially useful,” he says. Duncan MacCannell, a bioinformat- ics specialist at CDC in Atlanta, told Science that the sequences had been “actively shared and discussed with the public health com- munity.” He says CDC is working to submit the sequences to a public database.
New sequences probably won’t show that the virus is finding new ways to attack or spread, Rambaut says. Instead, the prize is a clearer picture of the outbreak. A cluster of closely related viruses might point to a hotspot of transmission, he says, while un- expectedly diverse sequences would suggest that many cases were going undetected. Sequence data could also help researchers tell whether there has been more than one animal-to-human introduction.
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