Ebola, research ethics, and the ZMapp serum


A Nigerian health official displays a leaflet explaining Ebola Virus Disease (Sunday Alamba/AP)

The ongoing West African Ebola outbreak has, after five months, finally captured global attention, in large part because in late July, three Americans contracted the virus. One, Liberian-American Patrick Sawyer, died in Lagos after flying from Togo. The other two U.S. citizens are health workers at a clinic in Liberia’s capital, Monrovia, who have since been transported for advanced care at Emory Hospital in Atlanta.

Monday brought news that to many seemed miraculous: the Americans being treated at Emory seemed to have been revived – and possibly saved – from Ebola thanks to an experimental serum, ZMapp, that was secretly transported to their bedsides in Monrovia. Dr. Kent Brantly, who had sensed that he was in the end stages of Ebola and about to die when he ingested the serum, was so much improved that he was able to walk from his ambulance into Emory with only minimal assistance. Missionary Nancy Writebol’s symptoms also improved, although it took two doses of ZMapp for her to experience improvement, whereas Brantly only required one.

The news of a possible cure for Ebola is heartening, but it left many observers with mixed reactions. Why were Brantly and Writebol the only Ebola patients to receive ZMapp? The optics of the situation were already bad enough: at great expense, two white Americans were whisked away to safety and a level of health care that simply cannot be provided on the fly in a Liberian hospital. The black Liberians they had been treating were left to see whether fate would save or kill them under the same substandard health care system they have always lived under.

That what now looks like a miracle cure was only given to the white Americans looks even worse. Why hadn’t anyone reached out to try the serum on Ebola patients sooner, especially if its potential to heal is so promising? Is the world of global public health really so biased toward the privileged that Americans get help while everyone else suffers? If nothing else, can we at least start giving ZMapp to as many Ebola-infected West Africans as possible?

There are no easy answers to these questions, and people of good will should be unsettled by the way this unfolded. That said, the dilemmas faced by scientists and public health workers with respect to using ZMapp are complex. Every U.S. researcher who works with human subjects, whether in the social or hard sciences, must abide by a set of strict protocols and regulations. Deviating from these norms can lead to being reprimanded, terminated from employment, and any number of other punitive outcomes. More importantly, it can also significantly harm research subjects, causing them physical and psychological suffering from which they may never recover or be compensated.

What’s at stake for researchers when it comes to ethical testing and deployment of a new treatment? The first and most important principle of ethical research is that the subjects (in this case, Ebola patients) are able to give meaningful informed consent. “Informed consent” means that an individual or community understands what is going to happen if they agree to take an experimental drug or be interviewed for a study or participate in a survey. In general, researchers have to fully inform subjects about what they will be taking, the risks of participation and non-participation, and how the data generated from the study will be used (ie, the findings might be published in an academic journal and promoted in a newspaper).

The trick to informed consent is that it has to be meaningful. It’s not enough to just tell subjects about the study; they need to understand what that means, and to be capable of saying or signing a document saying, “Yes, I understand, and I’m still willing to participate.”  This leads us to a second major concern for ethical research: the treatment of vulnerable populations. There are some groups of people who by definition are unable to give meaningful informed consent. These include children, institutionalized persons (prisoners and those confined to mental health institutions), and anyone else who might not be capable of understanding the full implications of their decision to participate in a study.

A Liberian suffering from Ebola would almost certainly be considered to be a vulnerable person by most research ethics boards.  Consider these issues.  Can someone who is gravely ill and who has never heard of the concept of “informed consent” really fully consider the implications of taking a drug like ZMapp?  Could he or she feel coerced because foreign doctors are the ones asking for consent?  Does the patient understand that the drug might not work, or might have very negative side effects down the road?  Add to this the dilemmas of cross-cultural communication, where misunderstanding is as likely as not, and it is very likely that “consent” becomes meaningless in the context in which the Ebola outbreak is happening.

Compounding these dilemmas is the fact that ZMapp has never before been tested in humans. It was given to Brantly and Writebol under a “compassionate use exemption,” an approval from the FDA that allows a drug that has not been fully tested to be used anyway when a patient may have no other way to survive than by taking the drug. That ZMapp seems to have helped Brantly and Writebol does not change the fact that researchers know almost nothing about how the drug works in humans.  It could be the case that the drug saves Ebola patients, but causes another health complication like cancer or dementia five years later. ZMapp might work differently in men than in women, or be more effective when given to the young than the old. It could save adults but kill children. We simply don’t know.

Figuring out these issues requires rigorous testing, which in the drug creation process is most commonly conducted through several rounds of clinical trials. The best studies are randomized control trials, in which some study participants get the real treatment (in this case, ZMapp) while others get a placebo, and researchers follow what happens to each subject to assess the effectiveness of the drug in different kinds of populations. Most Americans are familiar with and understand this concept; someone has to risk unknowingly taking the placebo so we can learn whether the actual drug works.

It is far from clear that citizens of developing countries understand randomized trials in the same way.  As lawyer Esther Chang noted in a 2002 paper, developing country participants in clinical trials often do not understand the concept of a placebo or may misunderstand informed consent forms. Journalist Howard French observed such problems firsthand in his observations of a 1997 clinical trial in Cote d’Ivoire of whether and how antiretroviral drugs could prevent transmission of HIV from mother to infant. Most social scientists who do research in developing countries – myself included – have similar stories of subjects not understanding why they are being asked to sign an informed consent form; in their minds, agreement to talk to me is consent. Signing a document also leaves a record, which many subjects fear might somehow be used against them by political authorities, foreign spies, or others who are up to no good.

Those fears are not entirely unfounded in some parts of the world where free speech is not a right subjects can take for granted. In the case of medical trials, ethical researchers are also aware of the long and terrible history of research – often on poor black people who were not asked to give informed consent – that has caused significant harm to study participants. From the Tuskegee syphilis experiment to Pfizer’s disastrous 1996 meningitis vaccine trial in Nigeria, unethical studies that victimize vulnerable persons of African origin abound. Nobody involved in discussions about ZMapp wants to repeat this situation, or to put West African Ebola patients who may or may not be able to meaningfully consent at risk for consequences no one can anticipate.

A final ethical issue concerns accountability when things do go horribly wrong with a drug trial. If Brantly or Writebol experience significant negative side effects from taking ZMapp, they will have avenues for legal recourse in U.S. courts, although these will be limited by the fact that they were able to give meaningful informed consent. Victims of the Pfizer debacle in Nigeria had to fight a lengthy and difficult legal battle to get compensation for their suffering, and there were major legal questions about whether Nigerians could sue a U.S. company in American federal courts. Legal recourse for poor Liberians, Sierra Leoneans, or Guineans would be an expensive and difficult task.

None of this means that ZMapp, if it can be manufactured in larger doses in a quick time frame, cannot be used on other Ebola patients as it was with Writebol and Brantly. The World Health Organization announced today that they are forming a panel of ethicists to consider whether and how ZMapp might be distributed among Ebola patients. There is no doubt in anyone’s mind that the urgency of Ebola, its high fatality rate, and the need to deliver effective treatment as quickly as possible must be taken seriously. Here’s hoping that the WHO ethicists can come to a quick conclusion, that ZMapp can be manufactured quickly, and that the drug will be responsibly distributed in a way that informs patients and their families to the fullest extent possible and allows researchers to learn more about how it works and doesn’t work in human populations. A cure for Ebola would be a wonderful thing indeed.

Laura Seay is an Assistant Professor of Government at Colby College. She studies African politics, conflict, and development, with a focus on central Africa. She has also written for Foreign Policy, The Atlantic, Guernica, and Al Jazeera English.
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