Ten years ago, a correspondence [1,2], signed by more than 70 championed ‘A global
initiative on sharing avian flu data’ (GISAID) [3], leading to the GISAID Initiative
in 2008. What started out as an expression of intent to foster international sharing
of all influenza virus data and to publish results collaboratively has emerged as
an indispensable mechanism for sharing influenza genetic sequence and metadata that
embraces the interests and concerns of the wider influenza community, public health
and animal health scientists, along with governments around the world. Today GISAID
is recognised as an effective and trusted mechanism for rapid sharing of both published
and ‘unpublished’ influenza data [4]. Its concept for incentivising data sharing established
an alternative to data sharing via conventional public-domain archives.
In 2006, the reluctance of data sharing, in particular of avian H5N1 influenza viruses,
created an emergency bringing into focus certain limitations and inequities, such
that the World Health Organization (WHO)’s Global Influenza Surveillance Network (now
the Global Influenza Surveillance and Response System (GISRS) [5]) was criticised
on several fronts, including limited global access to H5N1 sequence data that were
stored in a database hosted by the Los Alamos National Laboratories in the United
States (US) [6,7]. This data repository, set up with financial support from the US
Centers for Disease Control and Prevention (CDC) as a first attempt to share ‘sensitive’
data from affected countries, but was accessible only to those who were also providing
H5N1 sequence data. This limited-access approach restricted wider sharing of data
prior to publication, which was vital for broader understanding of the progress of
the emergent public and animal health threat. The need for greater transparency in
data sharing and for acknowledgement of those contributing samples from H5N1-infected
patients and animals and related genetic sequence data was not satisfied by sharing
data after formal publication via public-domain databases. Scientists charged with
the day to day responsibilities of running WHO Collaborating Centres (CCs) for Influenza,
National Influenza Centres and the World Organisation for Animal Health (OIE)/ Food
and Agriculture Organization of the United Nations (FAO) [8] reference laboratories,
were therefore eager to play a key role and provide scientific oversight in the creation
and development of GISAID’s data sharing platform that soon became essential for our
work.
A unique collaboration ensued, involving, in addition to members of WHO’s GISRS and
OIE/FAO reference laboratories, the wider influenza research community along with
officials in governmental institutions and non-governmental organisations. Facilitated
by a well-connected broadcast executive with background in licensing of intellectual
property, an agreement was drawn up on the sharing of genetic data to meet emergency
situations, without infringing intellectual property rights - the GISAID Database
Access Agreement (DAA). The DAA governs each individual’s access to and their use
of data in GISAID’s EpiFlu database [9]. It was this alliance between scientists and
non-scientists, with a diversity of knowledge and experience, involved in drawing
up an acceptable simple, yet enforceable, agreement which gained the trust and respect
of the scientific community and public health and animal health authorities.
The essential features of the DAA encourage sharing of data by securing the provider’s
ownership of the data, requiring acknowledgement of those providing the samples and
producing the data, while placing no restriction on the use of the data by registered
users adhering to the DAA. It essentially defines a code of conduct between providers
and users of data, cementing mutual respect for their respective complementary contributions,
and upholding the collaborative ethos of WHO’s GISRS, initially established 65 years
ago this year [5].
Launched in 2008, the EpiFlu database was of key importance in the response to the
2009 influenza A(H1N1) pandemic, allowing countries to readily follow the evolution
of the new virus as it spread globally [10]. Acceptance of the GISAID sharing mechanism
by providers and users of data, and the confidence of the influenza community, were
further illustrated in 2013 by the unprecedented immediate release of the genetic
sequences of Influenza A(H7N9) viruses from the first human cases, by Chinese scientists
at the WHO Collaborating Centre for Influenza in Beijing [11,12]. Such events reaffirmed
GISAID’s applicability to timely sharing of crucial influenza data. The subsequent
use of the sequence data to generate, develop and test candidate vaccine viruses by
synthetic biology within a few weeks also demonstrated how GISAID successfully bridged
this important ‘technological’ gap [13,14]. The paper by Bao et al. from Jiangsu province
of China published in this issue once again confirms the importance of the timely
sharing of data on the evolution of the A(H7N9) viruses for global risk assessment.
The authors analysed the recently isolated H7N9 viruses form the fifth wave in Jiangsu
province, and the results showed no significant viral mutations in key functional
loci even though the H7N9 viruses are under continuous dynamic reassortment and there
is genetic heterogeneity. These findings should help to reduce concerns raised, even
though the number of human infection with H7N9 virus increased sharply during the
fifth wave in China.
GISAID provides the data-sharing platform particularly used by GISRS, through which
sequence data considered by the WHO CCs in selecting viruses recommended for inclusion
in seasonal and pre-pandemic vaccines are shared openly and on which research scientists,
public and animal health officials and the pharmaceutical industry depend. Such openness
of the most up-to-date data assists in an understanding of and enhances the credibility
of the WHO recommendations for the composition of these seasonal and potential-pandemic
vaccines.
Furthermore, in promoting the prompt sharing of data from potential pandemic zoonotic
virus infections, as well as from seasonal influenza viruses, GISAID ensures a key
tenet of the WHO Pandemic Influenza Preparedness (PIP) Framework [15], highlighting
the critical role it plays in mounting an effective mitigating response. GISAID’s
ability to facilitate efficient global collaborations, such as the Global Consortium
for H5N8 and Related Influenza Viruses [16,17], is central to monitoring phylogeographic
interrelationships among, for example, H5 subtype viruses in wild and domestic birds
in relation to their incidence, cross-border spread and veterinary impact, and assessing
risk to animal and human health [18].
Traditional public-domain archives such as GenBank, where sharing and use of data
takes place anonymously, fulfil a need for an archive of largely published data; however,
that conventional method of data exchange notably has not been successful in encouraging
rapid sharing of important data in epidemic or (potential) pandemic situations, such
as those caused by Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola
viruses. While the GISAID EpiFlu database is hosted and its sustainability ensured
through the commitment of the Federal Republic of Germany [19], the establishment
of GISAID and development of the EpiFlu database was reliant to a large extent on
philanthropy of one individual and voluntary contributions and generosity of many
others, together with some initial financial provision by the US CDC and the German
Max Planck Society.
That GISAID has become accepted as a pragmatic means of meeting the needs of the influenza
community in part reflects the particular characteristics of influenza and the continual
need for year-round monitoring of the viruses circulating worldwide, essential for
the biannual vaccine recommendations and assessment of the risk posed by frequent
zoonotic infections by animal influenza viruses [20]. In the meantime, calls for an
equivalent mechanism to promote the timely sharing of data in other urgent epidemic
settings go largely unfulfilled [21,22]. A recent publication considered whether the
‘paradigm shift’ in data sharing by GISAID could be applied more generally to assist
in preparedness for and response to other emergent infectious threats, such as those
posed by Ebola virus [21] and Zika virus [23]. Such a trusted system could complement
and take full advantage of the latest advances in rapid sequencing of specimens in
the laboratory and in the field, for outbreak investigation [24].
Given the crucial importance of genetic data in improving our understanding of the
progress of an emergent, potentially devastating epidemic, the effectiveness of GISAID
in influenza pandemic preparedness is self-evident and provides important lessons
for future pandemic threats. While the genetic makeup and the necessary associated
data of the different viruses are distinct requiring separate databases/compartments
for unambiguous analysis, the modi operandi for sharing genetic data are generic and
the GISAID mechanism could be applied to other emerging pathogens. Indeed, the wider
implementation of such a data sharing mechanism should be key in concerted efforts
to contain spread of disease in animals and threats to human health, in realising
the concept of One Health.