By Julie Steenhuysen
CHICAGO, Nov 5 (Reuters) - Scientists across the United States say they cannot obtain samples of Ebola, complicating efforts to understand how the virus is mutating and develop new drugs, vaccines and diagnostics.
The problems reflect growing caution by regulators and transport companies about handling Ebola as well as the limited resources of West African countries which are struggling to help thousands of infected citizens.
Ten scientists from eight major research institutions contacted by Reuters reported they were unable to get Ebola samples in recent months.
Tulane University, one of the institutions, received samples this week, and the U.S. Centers for Disease Control and Prevention (CDC) said it has reached an agreement to get live specimens, but it is not clear if new supplies will satisfy demand, and transport remains challenging.
Ebola mutates as it spreads, and while few expect it to acquire the ability to transmit through air, for instance, scientists require a constant supply of fresh samples to track these changes. The samples hold up is not likely to delay the development of experimental treatments. But if the virus undergoes significant changes that go undetected, the drugs and tests might not work, researchers said.
Microbiologist and infectious disease expert Dr. Charles Chiu of the University of California, San Francisco, needs samples from Ebola patients to develop a new genetic test that could detect the disease in infected individuals before symptoms appear.
"No one really knows right now what has the virus mutated to or if it has mutated," he said. Without that research, "we're not going to be able to determine in advance whether or not it has changed to a form where it might evade diagnostic assays or might render current vaccines or drugs ineffective."
Scientists say Liberia, Guinea and Sierra Leone have been slow to release samples as they fight to contain the worst Ebola outbreak on record which has killed about 5,000 people.
Laurie Garrett, the senior fellow for global health at the Council on Foreign Relations in New York, said the issue is largely, and appropriately, about safe transport, especially in the wake of the recent mishandling of pathogens such as anthrax at U.S. government laboratories.
"All the companies working on vaccines, diagnostics and treatments are complaining about lack of access to viral samples," of Ebola, she said.
Erica Ollmann Saphire of the Scripps Research Institute in La Jolla, California, directs scientists working on Ebola treatments, such as the three-antibody cocktail ZMapp, made by privately-held Mapp Biopharmaceutical. She said in an e-mail she needs special cells from Ebola survivors but has not been able to get any.
Dr. James Crowe, director of the Vaccine Center at Vanderbilt University, is collaborating with Mapp on ZMapp, and has had problems as well. Crowe said he may soon get some samples from U.S. Ebola survivors through Emory University, after going to great lengths to get them.
Crowe said a mutation in a key area of the virus "could compromise the utility of the drug," adding that there is no evidence that such changes have occurred. Mapp did not respond to a request for comment.
Importing Ebola virus into the United States has always been tricky, said Dr. John Schieffelin of Tulane, who has treated Ebola patients in Sierra Leone.
It has become even more difficult since the case of Thomas Duncan, the first person diagnosed with Ebola in the United States, stoked fears that the country could see its own outbreak. Duncan died in a Dallas hospital on Oct. 8.
"You can divide the outbreak into pre-Dallas and post-Dallas," Schieffelin said. "Everybody has safety as a very, very high priority, which is great. But sometimes the fear and hysteria trumps science."
A RARE SUCCESS
This week, Tulane received a shipment of as many as 900 blood samples from Ebola patients in Sierra Leone, capping several weeks of effort. Tulane microbiologist Robert Garry believes the university's decade-long relationship with the Sierra Leone Ministry of Health and Sanitation was key to getting that access.
Even so, exporting the samples from Sierra Leone required approval from an ethics committee, the minister of health and the president. On the U.S. side, importing samples of Ebola required a permit from the CDC and passage through U.S. customs.
The researchers switched shipping companies after one refused to carry Ebola, missed a flight which did not have room for cargo, and had to bring dry ice to Africa to pack the samples, which were killed with a double shot of an inactivating agent, plus a shot of ethanol for good measure.
Tulane researchers will extract RNA from the samples and ship them to collaborators at Harvard University and the Broad Institute, which plan to sequence the genetic code of the virus and track the mutations taking place.
Earlier this year, Garry and several dozen colleagues from Harvard and Sierra Leone found that Ebola was mutating twice as fast in humans as in fruit bats which carried the virus. Their last sample was from June, and it is not clear what changes have occurred in the virus since then.
"You need to know how much of an adaptation the virus is making in people," if you want to treat and diagnose it, Garry said.
CDC spokesman Tom Skinner said that the agency has struck agreements with the three affected countries in West Africa and hopes to acquire live specimens in a matter of weeks. It then would try to share samples with other institutions.
"How much sharing will go on will depend on how many specimens we receive and finalizing details around getting permission to share from the affected countries," he said.
The lack of access to African samples has also caused a scramble for blood samples from the handful of U.S. patients who have survived, including Dallas nurse Nina Pham who treated Duncan, said Thomas Geisbert, a microbiologist at the University of Texas Medical Branch.
Geisbert has a $26 million grant from the National Institutes of Health to study experimental Ebola treatments. He works with leading Ebola drug developers Profectus BioSciences and Tekmira Pharmaceuticals Corp and is collaborating with Crowe at Vanderbilt for a next-generation antibody treatment for Mapp.
Tekmira did not respond to a request for comment. Profectus Chief Scientific Officer John Eldridge said the company had not encountered problems, but added that Geisbert should have a better understanding of the difficulties.
Geisbert does not think the delays in obtaining samples have held up the development of specific products. Most of these are based on samples from earlier Ebola outbreaks. But to confirm their effectiveness, it would be helpful to test Tekmira's TKM-Ebola and Mapp's ZMapp against the latest outbreak strains.
"There is no substitute for confirming activity against a live infectious virus," he said.
Geisbert managed to get blood samples gathered in March from Ebola survivors infected in Guinea, where the current outbreak started, but has none from Liberia or Sierra Leone. He has made several appeals to U.S. Ebola survivors and the hospitals that treated them, and enlisted Tekmira, but has not succeeded.
"It's crazy. You ask, and nobody responds," said Geisbert, who asked Reuters how to get in touch with Pham. (Additional reporting by Sharon Begley in New York; Editing by Michele Gershberg and Peter Henderson)