LONDON – As the Ebola virus grips an unprecedentedly wide swath of Africa, many are asking whether it is time to begin administering untested drugs and vaccines. Given that the disease can kill up to 90% of its victims – higher than the mortality rate from the bubonic plague – there seems to be little to lose from relaxing clinical norms. But the suggestion raises difficult ethical questions – and the urgency of the situation does not leave much time for deliberation.
One reason that there is no proven cure or vaccine for Ebola hemorrhagic fever is the wiliness of crossover diseases. These viruses are transmitted from animal populations, which can act as reservoirs where the pathogens can develop and mutate, making it difficult for researchers to keep pace with the diseases’ variations.
But another reason is pharmaceutical companies’ declining interest in manufacturing vaccines. Indeed, only four companies today make vaccines, compared to 26 companies 50 years ago. These firms know that the return on their investment will be relatively low, owing to the long lead-in time that results from slow manufacturing processes (though new, faster methods offer some hope).
Public distrust of vaccines has also played a major role in this decline. In the late 1990s, anti-vaccine sentiment manifested itself in a backlash against the measles, mumps, and rubella vaccine. Similarly, a 2004 New York Academy of Medicine survey indicated that twice as many people were worried about the side effects of the well-established smallpox vaccine as were concerned about the disease itself.
The comparative docility of infectious diseases like smallpox has contributed to a degree of complacency about the magnitude of the risks of refusing vaccination. When an epidemic actually begins, people quickly change their minds, and demand the rapid production and distribution of vaccines. That is probably a good thing, but it is also unrealistic.
The British pharmaceutical company GlaxoSmithKline recently announced that, together with the US National Institute of Allergy and Infectious Diseases, it is developing an experimental vaccine for Ebola. But it is just entering phase I clinical trials to test toxicity. With two more trial stages to go, the vaccine would not be ready for deployment before 2015.
The duration of the trial process has provoked complaints of excessive red tape. But such criticism is unfounded, given the potential of proposed drugs to cause serious illness or even death. Indeed, phase I trials – also called “first-in-man studies” – are extremely risky and ethically knotty, meaning that they must be handled with the utmost care.
In 2006, phase I trials of the drug TGN1412 had to be suspended when previously healthy volunteers developed multiple organ failure, with some barely escaping death. University College London pharmacologist Trevor Smart believes that they may never fully recover.
But what about when a population is already ill? In 1996, during a major meningitis epidemic in northern Nigeria, the drug company Pfizer supplied doctors with the oral antibiotic Trovan, which was being tested against another drug, ceftriaxone.
Eleven children died during the Trovan trial, and others were left permanently disabled. Still, the death rate in the Trovan trial was much lower than the rate from untreated meningitis, bolstering the case for administering untested Ebola drugs today.
In fact, the World Health Organization has already pronounced the use of the experimental serum ZMapp – a mixture of genetically engineered antibodies intended to help patients fight the disease – ethical. ZMapp never made it to human trials and is not yet licensed by the US Food and Drug Administration.
As it stands, only a few doses of ZMapp exist, and it will take months to produce even a modest supply. This raises another ethical dilemma: Who should receive such a scarce resource?
The first three doses of ZMapp were administered to the American medical missionaries Kent Brantly and Nancy Whitebol, who have recovered, and the Spanish priest Miguel Pajares, who has since died. Some offered a practical justification for the widely criticized selection of Brantly and Whitebol: It makes sense to treat health workers first, so that they can continue to help others. But this argument largely fell apart with the selection of the 75-year-old Pajares.
The credibility of claims that practicality drove the selection was, to some extent, revived by the decision to provide doses to three African doctors. In any case, the available supply of ZMapp has been exhausted.
It is important to note that even pragmatic arguments about rationing scarce medical resources can be highly controversial. During World War II, when army doctors were forced to ration doses of penicillin, they decided to give first priority to men with sexually transmitted diseases, who would be ready to return to the battlefield more quickly. But many contended that men who had been wounded in battle were more deserving.
Putting such a moral spin on the allocation of Ebola treatments, it could be argued that Africans should be selected over Westerners, because Africa’s health-care systems are less able to combat the disease. But one might also contend that Western medical workers deserve higher priority because they volunteered to expose themselves to the disease, in order to help those who had no choice.
Such arguments make reaching agreement virtually impossible. Worse, using social, rather than medical, criteria for rationing treatments is a slippery slope. One need only recall Seattle’s notorious “God” committee, which in the early 1960s allocated then-scarce kidney dialysis on the basis of criteria like earnings, church involvement, and even Scout membership. The use of social criteria for treatment allocation has had a bad name ever since – and rightly so.