Battling Ebola, Back to Basics
There have been 24 Ebola outbreaks since 1926—but the number of infections in the current epidemic exceeds all of them combined: 23,000 people ill, most of them in Guinea, Liberia, and Sierra Leone. Nearly 10,000 people have died. Though the infection and fatality rates both appear to have fallen—and international and media attention is trailing off—The New York Times has just reported a wave of new cases in the capital of Freetown, in Sierra Leone. Meanwhile, the healthcare systems of Guinea and Liberia struggle to recover.
Harvard Medical School held a symposium on Ebola yesterday that drew several hundred attendees for presentations about efforts to develop vaccines and therapeutics. Dean Jeffrey Flier, along with microbiology and immunobiology department chair John Mekalanos, introduced the event as a chance to assess the lessons of the crisis, approximately one year after it began.
“We know much less than we pretend to know” about the virus’s pathogenesis, said Jens H. Kuhn, virology lead at the National Institute of Allergy and Infectious Diseases, before laying out the many unknowns that surround the biological mechanisms of Ebola and its larger family of filoviruses. The recent outbreak triggered a spate of publications about filoviruses, he explained, yet little of that material was usefully rigorous; this is often because researchers will study one filovirus and then extrapolate their results, even though different strains are genetically distinct and thus exhibit very different behavior. “I actually don’t want you to look at this slide,” Kuhn said of a colorful chart that summarized current studies at the end of his presentation. “This slide means we have no clue.”
Effective patient care presents an entirely different challenge. “It’s not necessarily rocket science,” said Marshall Lyon, a physician and professor at Emory School of Medicine who helped to treat four of the outbreak’s U.S. cases, “but it is demanding.” Lyon spoke about the importance of assembling a multidisciplinary, communicative team—including physicians, nurses, lab and facilities staff, and others (Emory’s team numbered in the dozens)—as he detailed the hospital’s strategies, including protocols for protective gear and pre-positioning lab and cleaning equipment. “There’s nothing magic about taking care of these patients,” Lyon explained. “It’s all supportive care,” including fluid management and rehydration, electrolyte imbalance correction, and acute organ failure support.
Writing in the London Review of Books last October, Paul Farmer, Kolokotrones University Professor of global health and social medicine, had expressed a similar sentiment—that regardless of the current state of antivirals or other remedies, “You can’t stop Ebola without staff, stuff, space and systems.” That essay went on to argue that the severity of the epidemic in West Africa could be traced back to “grotesque and growing disparities in access to care,” a problem he elaborated on during his conference talk. Farmer noted that the most recent chain of transmission, reported a few weeks earlier, had a 100 percent mortality rate, saying that, “In my opinion, there’s no way that 11 out of 11 of those people would have died at Emory.”
Farmer advocated for the energies that had been poured into the emergency response to be re-directed to building a proper laboratory and medical delivery system. Even as Ebola slows, he pointed out, other “simple things” have worsened: infection rates for measles and pertussis have recently accelerated, for example, and the number of family-planning visits at local clinics has dropped.
Each of the three remaining sessions took up a different facet of the challenge of designing Ebola countermeasures. Researchers offered a detailed look at the most promising prospects for developing antibodies, vaccines, entry inhibitors, and polymerase inhibitors. Later in the afternoon, experts with perspectives from academia, industry, and government debated the institutional obstacles to the development of medicines: designing safe but rigorous efficacy studies pose one problem; then come funding challenges and regulatory hurdles, as researchers try to secure approval for each phase of clinical trials.
“We really shot ourselves in the foot” in several ways, said Gary Nabel ’75, G ’80, M.D. ’82, chief scientific officer of the multinational pharmaceutical company Sanofi. For example, a ban on the release of genetic information about the Ebola virus, and the classified status of its polymerase chain sequence, seriously hampered research efforts. “The law of unintended consequence plays out over and over again in Ebola research,” he warned.
Moreover, the gaps between commercial and academic research interests are creating a “perfect storm” for infectious disease, added Don Ganem ’72, M.D. ’77, head of infectious diseases research at Novartis. Without stable funding for late-phase trials, pursuing the development of therapeutics for infectious diseases like Ebola is unattractive to “big pharma” companies, he acknowledged. “The drugs are also extraordinarily difficult to make,” he added, and once on the market, they can’t command premium prices “any more than premium prices can apply to lettuce and milk at Safeway.” Meanwhile, academic microbiology may swiftly identify the target and pathway of infectious disease, but the field has neglected to train its talent in additional subjects necessary for drug development: medicinal chemistry, pharmacokinetics, or toxicology.
Opening the conference, the organizers had encouraged attendees to examine Ebola as a case study for the response to emerging outbreaks. The day’s debate over how the medical community could counter infectious disease more swiftly and effectively echoed Farmer’s morning remarks, in which he warned against “Ebola triumphalism.” The need for basic care for patients—and basic research by scientists—both attest to what he called “the humility we need” when confronting the ravages of this, or the next, epidemic.