The 12-year-old serious communicable disease unit at Emory University Hospital hadn’t gotten much attention until last week, when it began treating two Americans infected with the Ebola virus with an experimental monoclonal antibody called ZMapp. No comparable facilities exist in any of the four West African countries that are experiencing the largest known outbreak of Ebola, and ZMapp and the handful of other Ebola drugs in development are unavailable in those countries. What’s more, very little ZMapp is available at all. On Tuesday morning Mapp Biopharmaceuticals, the company that makes the drug, said on its website that its supply has been exhausted.
Much has been made of the ethical and moral considerations of treating some but not all Ebola patients with these experimental drugs. Some commentators contended that it was racist to treat white Americans and not black West Africans. On the subject of administering experimental drugs whose effectiveness is not fully proven, the World Health Organization issued a statement on Monday saying that it had convened a group of consultants to evaluate the situation and that they concluded that it was ethical “to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.”
Which, if any, of these facts are morally troubling?
Deadly and rare
One point to remember about Ebola is that it is utterly deadly but remains very rare. Since its identification in 1976 by the Belgian scientist Peter Piot, Ebola has claimed approximately 2,500 lives — almost half of those in the current outbreak. Malaria, acute respiratory infections and diarrheal diseases kill many millions of people each year. There is so little financial incentive to develop vaccines or cures for rare infectious diseases that the research leading to ZMapp was funded by the U.S. Department of Defense under the aegis of the Defense Threat Reduction Agency, which, among its myriad tasks, works to minimize the danger from bioweapons. This differential allocation of research resources might be unfortunate, but it is not morally wrong because the disease affects far fewer people than other comparably serious illnesses.
It is true that the nearly 1,000 people who have died during this outbreak have been black Africans, while Nancy Writebol and Kent Brantly, the two Americans receiving treatment, are white health care workers who were transported from Liberia to the U.S. at considerable expense. Despite what some critics charge, the race and occupation of Writebol and Brantly are ethical red herrings, not ethical red flags. A large quantity of a safe and effective Ebola drug preferentially withheld from black African nonprofessionals would constitute a grave injustice, but that is not what has happened, because there is simply not much of anything to be withheld. Writebol and Brantly have clearly benefited from being Americans employed by a Christian charity with a proactive vice president of program and government relations. But their treatment in Atlanta is not tantamount to the devaluing of Africans’ lives.
Putting aside the ZMapp recipients’ race and nationality, an additional moral concern stems from the fact that ZMapp is genuinely experimental. Mapp Biopharmaceuticals has tested the drug in nonhuman primates but has not published the results of those studies. Its use in Atlanta is its first in human beings. Typically in the U.S., new drugs must survive rigorous testing. Phase one trials, using healthy volunteers, determine the safety, tolerability and pharmacokinetics of new drugs. Phase two trials have a larger subject pool and aim to establish efficacy. In phase three trials, the new drug’s efficacy is compared with existing alternatives. All participants in drug trials must give their informed consent — at the very least being made aware of the risks associated with the medication. We assume that Brantly and Writebol properly consented to being given ZMapp, even though they are receiving the drug under the FDA’s compassionate use exception. Their alternative being almost certain death, the choice is understandable.
If the ethical guidelines for human subject research have any purpose and meaning, it is precisely in cases like these.
But suppose, for the sake of argument, that large quantities of a not yet fully tested Ebola drug did exist. Would the manufacturer be wrong not to ship it to affected areas? The safety, tolerability and efficacy of the drug are not known. While scientists might welcome the opportunity to try out the product on large numbers of natural subjects — that is, people already suffering from the disease the drug is designed to treat — such research is constrained by internationally recognized standards regarding work with human subjects. The World Health Organization has always emphasized that ethical standards governing clinical trials must be respected, even in the midst of a terrible outbreak.
The point here is that we should not to be distracted by the exigencies of the present situation. As the WHO has declared, the Ebola outbreak in West Africa is a serious global public health emergency. But it is not a singularity. Ebola has always been known to be infectious and deadly. What was not known — and could not have been known — is when and where the virus would show up again and in what numbers.
This kind of uncertainty, present in many life-or-death scenarios, does not justify the suspension of procedures and protocols already thought through and designed to protect people from harm or exploitation in the very cases most likely to lead to it. In other words, if the ethical guidelines for human subject research have any purpose and meaning, it is precisely in cases like these. Constraints made in times of nonemergency protect against well-intentioned actions undertaken in emergencies that can lead to the exploitation of vulnerable people (very sick people) and cause serious harm.
But suppose, for the sake of argument, that large quantities of the not-yet fully tested Ebola drugs did exist. Would the U.S. and Canadian manufacturers act wrongly in not shipping them to affected areas? The safety, tolerability, and efficacy of these drugs are not known. And while scientists might welcome the opportunity to try out their products on large numbers of ‘natural’ subjects – that is, people already suffering from the disease the drug is designed to treat – such research is constrained by internationally recognized standards regarding work with human subjects. In a press conference last week, Margaret Chan, the director-general of the World Health Organization, emphasized that ethical standards governing clinical trials must be respected, even in the midst of this terrible outbreak.
The point here is that we should not to be distracted by the exigency of the present case. As the WHO has declared, the Ebola outbreak in west Africa is a serious global public health emergency. But it is not a singularity. Ebola has always been known to be infectious and deadly. What was not known, and in fact could not have been known, is when and where the virus would show up again and in what numbers.
This kind of uncertainty, present in many life and death scenarios, does not justify the suspension of procedures and protocols already thought through and specifically designed to protect people from harm and exploitation in the very cases in which we are most likely to cause it. In other words, if the ethical guidelines for human subject research have any purpose and meaning, it is precisely in cases like this one. Constraints made in times of non-emergency protect against well-intentioned actions undertaken in ‘emergencies’ that can lead to the exploitation of vulnerable people (very sick people) and cause serious harm.
The ultimate ethical test
In addition, the risk associated with participating in clinical trials is partly justified by the real possibility that researchers will learn something new. Even if experimental medications were available to be shipped en masse to West Africa, there would be no way of quickly setting up the kind of controls needed to test their efficacy. It would be patently unethical, for example, for one group of infected patients to receive an experimental drug while another is given a placebo (as is required by the gold standard double blind clinical trial).
Given the scarcity of the relevant drugs, it’s important not to lose sight of the fact that these questions are largely moot. Moreover, with respect to medicines that are known to be safe and effective in the treatment of highly infectious diseases such as smallpox and influenza, bioethicists and public health officials have thought through the ethical issues regarding allocation priorities in the case of a pandemic. Ethically defensible guidelines already exist, and if there were safe, effective and available drugs against Ebola, they would undoubtedly be followed.
Right now, all that can realistically be done is to contain the disease. This work is far removed from fancy bench science or lucrative research and development. It requires the painstaking identification and tracking of people who could be infected. It concerns the provision of cheap and readily available supplies such as rubber gloves, face masks and bottles of disinfectant. It also requires facilities that allow for the necessary isolation of infected individuals and provide supportive care for those whose deaths are inevitable.
Infectious diseases remind us how intimately connected human beings are. In declaring the Ebola outbreak a global public health emergency, the WHO has provided the rhetorical platform and the necessary moral suasion to get richer nations to help. It is not an empty gesture. The WHO’s director-general, Dr. Margaret Chan, correctly contextualized the outbreak and what can be done about it in terms of “collective health security.” Morally, the worlds’ citizens are in this together.
The media is bristling with stories and commentary on the outbreak. The U.S. Food and Drug Administration has fast-tracked Ebola vaccine development and has revised a clinical hold on phase one trials of TKM Ebola, a type of anti-Ebola drug different from ZMapp. Can and will this momentum be sustained, or will it taper off when — perhaps months from now — the outbreak has been contained?
That will be the real test of our ethics regarding the Ebola outbreak. What the U.S. does in the future will reveal our commitment to black Africans who live in remote areas of countries most of us cannot locate on a map.