In mid-July, Mapp Biopharmaceuticals, a small, privately held biotech firm based in San Diego, inked a deal to finalize the commercialization of an experimental drug known as ZMapp, a cocktail of three lab-created antibodies that, when combined, can do what no antibody—naturally occurring or otherwise—had been proven to do just several years ago: neutralize the Ebola virus.
Before this week, the drug was narrowly known, mostly by industry watchers and researchers. That changed on Monday, when it was reported that ZMapp had been given to Kent Brantly, a missionary doctor from Texas who contracted Ebola while working at ELWA hospital, in Monrovia, Liberia. According to CNN, "Brantly was able to walk into Emory University Hospital in Atlanta after being evacuated to the United States last week." Nancy Writebol, a missionary who worked in the same hospital, reportedly was also given ZMapp and arrived in Atlanta on Tuesday. Prior to these doses, the drug had never been tested in human subjects.
The inequality in care couldn't be starker. When a doctor and aid worker from the United States are stricken with a horrific disease, an erstwhile unknown cure is sent from freezers at the National Institutes of Health in suburban Washington, D.C., to a hospital on the other side of the world, and a Gulfstream jet outfitted for medevac is arranged to deliver them to one of the world’s premier medical centers. But when two Liberian nurses working at the same hospital are stricken with the same disease, they are treated with the standard of care that other affected Africans—those lucky enough to receive any medical attention at all—have been afforded for the past seven months: saline infusions and electrolytes to keep them hydrated.
This year’s outbreak has now claimed close to 900 lives, all but one occurring in Guinea, Sierra Leone, and Liberia. Until this outbreak, only 1,500 deaths had been attributed to Ebola over the past 37 years.
The Obama administration has not said whether it will allow ZMapp to go into production. Mapp Biopharmaceuticals published a statement to their website late Monday stating that the company is working “with appropriate government agencies to increase production as quickly as possible.” (An executive at BioProcessing, a Kentucky firm that produces at least one component of ZMapp, told an industry publication last August that his company can produce the proteins for ZMapp in two weeks.)
Would the mass production of ZMapp be underwritten by a major pharmaceutical firm, given that it's unlikely to generate a return on the investment? Will the U.S. government, or other affluent nations, step in to fund the enterprise? And is there a reason to expect that funds would be mobilized for an untested drug when they have not been forthcoming for basic protective equipment and other simple tools that could significantly boost the survival rate of infected people and reduce risk to healthcare workers?
And if mass production of ZMapp isn't imminent, why aren't doctors of Ebola patients even attempting a less-costly, relatively simple alternative to the drug?
It was initially reported by Samaritan’s Purse that Brantly had not been given ZMapp but instead received convalescent therapy, which involves transfusing blood from someone who has survived the current outbreak to those infected by the disease. The technique was first reported in the medical literature in 1977, alongside one of the first articles to describe Ebola. The piece, which appeared in the British Medical Journal, explains how a London scientist, working to isolate the virus in blood samples taken from those infected in Zaire, accidentally pricked his thumb through a protective rubber glove. Six days later, he came down with the disease. Blood taken from survivors was treated at 140 degrees Fahrenheit to ensure no active aspects of the virus remained, and was then transfused to the researcher.
The man’s temperature peaked at 104 degrees Fahrenheit on the fourth day of his illness, and he suffered severe vomiting, diarrhea, and a rash covering his body. His mental state deteriorated sharply. Three days later, he turned the corner, and went on to a full recovery.
Convalescent therapy was employed again in 1995 on a small group of patients during an outbreak in present-day Democratic Republic of Congo. “We treated eight patients and seven of them survived,” Dr. John-Jacques Muyembe, a professor of medicine in Kinshasa and a researcher with the Pasteur Institute, told me. The overall death rate for the outbreak was 80 percent; in the test group, it was 12.5 percent. The paper Muyembe and his colleagues published contains data on viral loads in the blood of six patients treated with the therapy. Five of them cleared the Ebola antigen within four days.
“I am also astonished why they do not use this technique in the field," Muyembe said about the current outbreak. "If I was there I would use it.” The therapy, he explained, does not require extensive infrastructure or knowledge. “They need no additional resources. They need only what they are doing every day. You have to test against HIV, Hepatitis, and Typhus, it is what they are doing usually in the blood transfusion center. It is not expensive.”
Muyembe said that the failure to replicate the success of the therapy in animal models was partly why the treatment has not been adopted more broadly. “At that time," he said, referring to the 1995 outbreak, "people from CDC told us that the antibodies as such do not protect in their experience with monkeys in the lab. In the lab they did not obtain protection, so it is why this is not used in the field.”
There are a number of reasons to be skeptical of the efficacy of convalescent therapy. Doctors Without Borders, for instance, has not adopted the technique, as it's not approved by the World Health Organization. And it’s unlikely convalescent transfusions have sufficient quantities of antibody to confer a passive immunity—the type of treatment used in the case of rabies bites, in which blood is pooled from a range of donors and antibodies are concentrated into a high-titer dose. But it’s possible that the transfusions, both by exposing the body to inactive forms of the virus and providing an additional supply of proteins necessary to stop bleeding, can provide a jumpstart of sorts at a critical moment.
Moreover, when an outbreak has a mortality rate greater than 70 percent, and the overall technical requirements for the therapy—equipment to transfuse the blood and screen it for other diseases—is available, and experimental drugs only arrive when citizens from the most affluent nation on earth contract the disease, why not try? What, in the end, is the risk of transfusing blood to patients likely to die of hemorrhagic shock?
Brantly and Writebol have unrivaled medical support available to them. Modern medicine can effectively replace many of their bodies’ critical functions to give their immune systems time to launch an effective response. Kidneys can be supplanted with dialysis and plasmapheresis, a technique to separate red blood cells from surrounding serum and clean the blood of toxins. Antiviral medications and a range of drugs to maintain blood pressure and adequate blood supply to organs will be at their attending physicians’ fingertips. And the risk of secondary infections, a major issue for those undergoing treatment in the developing world, will effectively be eliminated.
The Liberian nurses whom worked with Brantly and Writebol will not see such treatment. Neither ZMapp nor a Gulfstream jet will be sent for them. And ELWA hospital, where all four worked, is now shuttered. It was closed late last week. According to a doctor there, the facility ran short on protective clothes for the workers.