Combating a disease of unknown cause is a daunt- ing task. One hundred years ago, a pandemic of poorly understood etiology and transmissibility spread worldwide, causing an estimated 50 mil- lion deaths. Initially attributed to Haemophilus influenzae, it was not until the 1930s that an H1 subtype was identified as the causative strain.
Subsequent influenza pandemics in 1957, 1968, and
2009 did not approach levels of
morbidity and mortality comparable to those of the 1918 “
Spanish flu,” leaving unanswered
for almost a century questions
regarding the extraordinary
virulence and transmissibility of
this unique strain. Technological
advances made reconstruction
of the 1918 virus possible; now,
continued research, vaccine development, and preparedness
are essential to ensure that such
a devastating public health event
is not repeated.
Over the past 20 years, studies
of individual genes and the fully
reconstructed live 1918 virus
have identified numerous features that likely contributed to
its robustness and rapid global
spread. Importantly, this research has often been conducted
in tandem with viral isolates
from recent human and zoonotic
sources, enabling insights from
the 1918 virus to inform evaluations of current pandemic risk. As we now know, wild
birds are the natural reservoir for influenza A viruses.
With extensive antigenic and genetic diversity inherent among influenza virus surface proteins, a strain to
which humans are immunologically naïve could jump
the species barrier at any time. A(H5N1) viruses and,
more recently, A(H7N9) viruses, are two such examples.
However, swine are also recognized as a “mixing vessel”
for influenza viruses, and over the past two decades,
there has been an increase in human cases following
exposure to infected pigs. There is clearly, and alarmingly, a vast diversity of zoonotic sources of influenza A
viruses that could acquire a transmissible phenotype in
humans and cause a pandemic.
What is our readiness today? Many international
health agencies and research laboratories collaborate to
track influenza virus evolution, evaluate antigenic drift
among circulating and vaccine strains, and sequence
viral genes to advance surveillance and preparedness.
The production of improved vaccines and diagnostic
tools, and better access to therapeutic agents represent
resources that were not available a century ago. But influenza viruses are moving targets, and a pandemic virus could nevertheless emerge with as little warning in
2018 as in 1918. As evidenced by
this current flu season, influenza
viruses can rapidly acquire mutations that evade our most recent
vaccine formulations. A universal,
broadly protective influenza vaccine for seasonal epidemics—a
goal of intense research efforts—
would improve our preparedness
for subsequent pandemics.
How, then, can we best study
emerging pandemic threats?
Looking to the past, elucidating
the role of specific molecular determinants that confer virulence
and transmissibility of prior pandemic viruses is one approach.
But we must also look to the
future. Advances in next-generation sequencing are improving our understanding of virus
diversity. Investments in global
partnerships and laboratory capacity worldwide are strengthening surveillance networks and
diagnostic capabilities, and are
also facilitating the identification of new viruses in humans and animals. The recent
lifting of the U.S. moratorium on gain-of-function research on potential pandemic viruses further illustrates
the contribution of unconventional, but responsible, research strategies to readiness.
Philosopher George Santayana pointed out, “Those
who cannot remember the past are condemned to repeat it.” We are no doubt more prepared in 2018 for an
infectious disease threat than in 1918. But it is critical
to remember that preparation only stems from a global
commitment to share data about viral isolates, support
innovative research, and dedicate resources to assess
the pandemic risk of new and emerging influenza viruses from zoonotic reservoirs.
–Jessica A. Belser and Terrence M. Tumpey
The 1918 flu, 100 years later
Jessica A. Belser is
in the Influenza
GA 30333, USA.
Tumpey is chief of
Branch in the
of the CDC,
Atlanta, GA 30333,
“How, then, can
we best study emerging
SCIENCE sciencemag.org 19 JANUARY 2018 • VOL 359 ISSUE 6373 255