By Chris Healey
The deadliest and most pervasive Ebola outbreak in history is underway in Africa. As of August 8, the World Health Organization reported 1134 confirmed cases of Ebola in Guinea, Liberia, Nigeria, and Sierra Leone with 622 confirmed deaths.
Two Americans, Kent Brantly and Nancy Writebol, contracted Ebola while helping contain the epidemic in Africa. Both were flown to isolation units in Atlanta’s Emory University Hospital after receiving an experimental treatment called ZMapp. Brantly and Writebol’s condition is reportedly improving because of the drug.
ZMapp is the experimental brainchild of several pharmaceutical companies and their collaboration with the U.S. and Canadian governments. It is a combination of three antibodies determined to be the best components of two experimental Ebola treatments: MB-003 and ZMAb.
MB-003 is composed of a monoclonal antibody and an immune system stimulant. The monoclonal antibody binds to Ebola virus surface proteins to form a structure easily recognized as a threat by the host’s immune system. Mimicry allows the immune system stimulant to produce an inflammation-like response without causing tissue damage, serving to amplify immune response without damaging the host.
ZMAb, a combination of mouse-derived antibodies, inactivates Ebola virus surface proteins necessary for host cell entry. If Ebola virus cannot enter a host cell, it cannot cause illness. For higher efficacy, ZMAb antibodies target different parts of the surface proteins, making viral adaptation to the antibodies difficult.
ZMapp attracted much attention because it was used without being tested. Mapp Biopharmaceutical was preparing to enter Phase 1 clinical trials prior to the Ebola outbreak. Use of ZMapp in lieu of clinical trials is permitted by FDA regulations allowing drugs currently, or not at all, involved in clinical trials to be used in extenuating circumstances where no other pharmaceutical is appropriate.
ZMapp is not the first untested pharmaceutical to be used against Ebola in humans. In 2009, a researcher in Germany accidently exposed herself to Ebola virus when she pricked herself with an ebola-contaminated needle during a laboratory experiment. Within 48 hours, she was given an experimental Ebola vaccine never before used in humans. After 21 days, physicians prepared to discharge her from a Hamburg, Germany hospital because she had not developed any symptoms.
It is unclear if the vaccine prevented illness, or if the needle stick simply didn’t infect her with Ebola. Regardless, she produced Ebola virus antibodies after vaccine administration, indicating the vaccine produced an immune response.
When use of ZMapp was first reported, it was hailed in stories circulated by CNN as a “secret” and “top-secret” serum. However, current versions of the story now portray the serum as an “experimental drug.” It is unclear if the original reports of the serum’s secrecy were in error.
However, development of secret therapeutics is not farfetched. Classified treatments could conceivably serve national security interests.
State-sponsored bioweapon programs, for example, could use knowledge of existing therapeutics, such as those kept in the strategic national stockpile, to engineer biological agents resistant to available therapeutics. Such a tactic would cripple U.S. public health response to any weaponized agent. If ZMapp truly was classified, the U.S. may have been protecting the drug’s therapeutic mechanisms from those who would seek to overcome them.
Although withholding treatments would benefit the U.S., it raises ethical concerns. Some could argue treatment sequestration provides little benefit outside the U.S. A novel, effective treatment withheld in preparation for an attack –that may never occur– could be used in the present to treat the sick.
The merits of transparency must be weighed against interests of national security. For ZMapp, if it was classified, two American candidates for the drug were enough to bring it into the public domain.
Image Credit: International Business Times